Izvorni kôd stranice BRCA1

{{Infokutija gen}}
'''Protein osjetljivosti na rak dojke tip 1''' je [[protein]] koji je kod [[ljudi]] [[kodon|kodiran]] [[gen]]om '''BRCA1'''.<ref>{{cite web | url = http://www.healthcentral.com/breast-cancer/c/78/9925/brca1-brca2 | vauthors = Hamel PJ | title = BRCA1 and BRCA2: No Longer the Only Troublesome Genes Out There | publisher = HealthCentral | date = 29. 5. 2007 | access-date = 2. 7. 2010}}</ref> [[Ortolozi]] su česti kod drugih [[kičmenjaci|kičmenjačkih]] vrsta, dok [[genom]]i [[beskičmenjak]]a mogu imati srodni gen.<ref name="Ensembl">{{cite web |title=BRCA1 gene tree |url=http://www.ensembl.org/Multi/GeneTree/Image?gt=ENSGT00440000034289 |publisher=Ensembl}}</ref> '' BRCA1 '' je ljudski [[gen supresije tumora]] <ref name="pmid10193517">{{cite journal | vauthors = Duncan JA, Reeves JR, Cooke TG | title = BRCA1 and BRCA2 proteins: roles in health and disease | journal = Molecular Pathology | volume = 51 | issue = 5 | pages = 237–47 | date = oktobar 1998 | pmid = 10193517 | pmc = 395646 | doi = 10.1136/mp.51.5.237 }}</ref><ref name="pmid15546503">{{cite journal | vauthors = Yoshida K, Miki Y | title = Role of BRCA1 and BRCA2 as regulators of DNA repair, transcription, and cell cycle in response to DNA damage | journal = Cancer Science | volume = 95 | issue = 11 | pages = 866–71 | date = novembar 2004 | pmid = 15546503 | doi = 10.1111/j.1349-7006.2004.tb02195.x | s2cid = 24297965 | doi-access = free }}</ref> (poznat i kao [[domarski gen]]) i odgovoran je za [[popravak DNK]].<ref name="CAP">{{cite web | url = http://www.cap.org/apps/cap.portal?_nfpb=true&cntvwrPtlt_actionOverride=%2Fportlets%2FcontentViewer%2Fshow&_windowLabel=cntvwrPtlt&cntvwrPtlt{actionForm.contentReference}=cap_today%2Ffeature_stories%2F0906BRCA.html&_state=maximized&_pageLabel=cntvwr | title = BRCA: What we know now | vauthors = Check W | publisher = College of American Pathologists | date = 1. 9. 2006 | access-date = 23. 8. 2010}}</ref>

BRCA1 i [[BRCA2]] su nepovezani proteini,<ref name="Irminger-Finger_2016">{{cite journal | vauthors = Irminger-Finger I, Ratajska M, Pilyugin M | title = New concepts on BARD1: Regulator of BRCA pathways and beyond | journal = The International Journal of Biochemistry & Cell Biology | volume = 72 | pages = 1–17 | year = 2016 | pmid = 26738429 | doi = 10.1016/j.biocel.2015.12.008 | doi-access = free }}</ref> ali oba se normalno eksprimiraju u ćelijama [[dojka|dojke]] i drugom tkivu, gdje pomažu u popravljanju oštećene [[DNK]] ili uništavanju ćelija, ako DNK nije moguće popraviti. Oni su uključeni u popravak [[hromosom]]skog oštećenja s važnom ulogom u nepogrešivim [[popravak DNK|popravcima]] prekida dvolančana [[DNK]].<ref name="Friedenson2007">{{cite journal | vauthors = Friedenson B | title = The BRCA1/2 pathway prevents hematologic cancers in addition to breast and ovarian cancers | journal = BMC Cancer | volume = 7 | pages = 152–162 | date = august 2007 | pmid = 17683622 | pmc = 1959234 | doi = 10.1186/1471-2407-7-152 }}</ref><ref name="scivee.tv">{{cite web | url = http://www.scivee.tv/node/6090 | title = Breast cancer genes protect against some leukemias and lymphomas | vauthors = Friedenson B | date = 8. 6. 2008 | format = video | publisher = SciVee }}</ref> Ako su BRCA1 ili BRCA2 sami oštećeni [[BRCA mutacija|BRCA mutacijom]], oštećena DNK se ne popravlja pravilno, a to povećava rizik za [[rak dojke]].<ref name="urlBreast and Ovarian Cancer Genetic Screening">{{cite web | url = http://www.pamf.org/health/guidelines/geneticscreening.html | title = Breast and Ovarian Cancer Genetic Screening | publisher = Palo Alto Medical Foundation | access-date = 11. 10. 2008| archive-url= https://web.archive.org/web/20081004080235/http://www.pamf.org/health/guidelines/geneticscreening.html| archive-date= 4. 10. 2008 | url-status= live}}</ref><ref name="pmid17683622">{{cite journal | vauthors = Friedenson B | title = The BRCA1/2 pathway prevents hematologic cancers in addition to breast and ovarian cancers | journal = BMC Cancer | volume = 7 | page = 152 | year = 2007 | pmid = 17683622 | pmc = 1959234 | doi = 10.1186/1471-2407-7-152 }}</ref> ''BRCA1'' i ''BRCA2'' opisani su kao "geni osjetljivosti na rak dojke" i "proteini osjetljivosti na rak dojke". Prevladavajući [[alel]] ima normalnu funkciju supresije tumora, dok mutacije s visokom [[interakcija gena|penetrabilnošću]] u ovim genima uzrokuju gubitak funkcije supresije tumora, što korelira s povećanim rizikom od raka dojke.<ref name="O'Donovan_2010">{{cite journal | vauthors = O'Donovan PJ, Livingston DM | title = BRCA1 and BRCA2: breast/ovarian cancer susceptibility gene products and participants in DNA double-strand break repair | journal = Carcinogenesis | volume = 31 | issue = 6 | pages = 961–7 | date = april 2010 | pmid = 20400477 | doi = 10.1093/carcin/bgq069 | doi-access = free }}</ref>

BRCA1 se kombinira s drugim supresorima tumora, senzorima oštećenja DNK i pretvaračima signala da bi stvorio veliki kompleks multijedinica proteina poznat kao BRCA1-asocirani kompleks za nadzor genoma (BASC).<ref name = pmid10783165/> Protein BRCA1 povezuje se s [[RNK-polimeraza II|RNK-polimerazom II]], te putem [[C-terminal]]nog domena takođe komunicira sa kompleksima [[histon-deacetilaza]]. Dakle, ovaj protein ima ulogu u transkripciji i [[popravak DNK|popravljanju]] prekida dvolančane DNK<ref name = "pmid17683622" /> [[ubikvitin]]aciji, [[transkripcijska regulacija|transkripcijskoj regulaciji]], kao i drugim funkcijamaa.<ref name=Starita2003>{{cite journal | vauthors = Starita LM, Parvin JD | title = The multiple nuclear functions of BRCA1: transcription, ubiquitination and DNA repair | journal = Current Opinion in Cell Biology | volume = 15 | issue = 3 | pages = 345–350 | year = 2003 | pmid = 12787778 | doi = 10.1016/S0955-0674(03)00042-5 }}</ref>

Metodi za ispitivanje vjerovatnoće pacijenta sa mutacijama u ''BRCA1'' i ''[[BRCA2]]'' koje uzrokuju rak obuhvaćene su [[Biološki patent|patentima]] u vlasništvu ili pod kontrolom ''Myriad Genetics''. Myriadov poslovni model nuđenja dijagnostičkog testa vodio je isključivo od toga da je 1994. bio ''startup'' kompanija, koja je bila javna kompanija sa 1.200 zaposlenih i oko 500 miliona dolara godišnjeg prihoda u 2012.;<ref>[http://investor.myriad.com/index.cfm Myriad Investor Page—see "Myriad at a glance"] {{Webarchive|url=https://web.archive.org/web/20121018224334/http://investor.myriad.com/index.cfm |date=18. 10. 2012 }}.</ref><ref>Webarchive|url=https://web.archive.org/web/20121018224334/http://investor.myriad.com/index.cfm |date=2012-10-18 }} accessed October 2012</ref> to je također dovelo do kontroverze oko visokih cijena i nemogućnosti dobivanja drugih mišljenja od drugih dijagnostičkih laboratorija, što je zauzvrat dovelo do značajne tužbe ''Udruženja za molekulsku patologiju'' protiv ''Association for Molecular Pathology v. Myriad Genetics''.<ref name="SchwartzNYTimes">{{cite web |url= https://www.nytimes.com/2009/05/13/health/13patent.html |title= Cancer Patients Challenge the Patenting of a Gene | vauthors = Schwartz J |date= 12. 5. 2009 |id= Health |work=The New York Times}}</ref>

== Otkriće ==
Prve dokaze o postojanju gena koji kodira enzim za obnavljanje DNK, uključenog u osjetljivost na rak dojke pružio je laboratorij [[Mary-Claire King]] na ''University of California, Berkeley'', 1990.<ref name="pmid2270482">{{cite journal | vauthors = Hall JM, Lee MK, Newman B, Morrow JE, Anderson LA, Huey B, King MC | title = Linkage of early-onset familial breast cancer to chromosome 17q21 | journal = Science | volume = 250 | issue = 4988 | pages = 1684–9 | date = decembar 1990 | pmid = 2270482 | doi = 10.1126/science.2270482 | bibcode = 1990Sci...250.1684H }}</ref> Četiri godine kasnije, nakon međunarodne utrke za pronalaženje ,<ref>[http://scienceblog.cancerresearchuk.org/2012/02/28/high-impact-science-tracking-down-the-brca-genes-part-1/ High-Impact Science: Tracking down the BRCA genes (Part 1)] {{Webarchive|url=https://web.archive.org/web/20160220074818/http://scienceblog.cancerresearchuk.org/2012/02/28/high-impact-science-tracking-down-the-brca-genes-part-1/ |date=20. 2. 2016 }} – Cancer Research UK science blog, 2012</ref> gen su 1994. godine klonirali naučnici sa Univerziteta u Utahu, Nacionalnog instituta za nauke o zdravlju i životnoj sredini (NIEHS) i ''Myriad Genetics''.<ref name="pmid7545954">{{cite journal | vauthors = Miki Y, Swensen J, Shattuck-Eidens D, Futreal PA, Harshman K, Tavtigian S, Liu Q, Cochran C, Bennett LM, Ding W | title = A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1 | journal = Science | volume = 266 | issue = 5182 | pages = 66–71 | date = oktobar 1994 | pmid = 7545954 | doi = 10.1126/science.7545954 | bibcode = 1994Sci...266...66M | doi-access = free }}</ref>

== Lokacija gena ==
 [[slika:BRCA1_en.png|thumb|180px]]
Ljudski gen ''BRCA1'' nalazi se na dugom (q) kraku [[hromosom 17|hromosoma 17]] u području 2, opseg 1, između [[bazni par|baznih parova]] 41,196.312 i 41,277.500 (Build GRCh37/hg19)<ref>[http://genome.ucsc.edu/cgi-bin/hgTracks?db=hg19&singleSearch=knownCanonical&position=BRCA1 (map)].</ref>[[Nacionalni centar za biotehnološke informacije]], SAD, Nacionalna biblioteka za medicinu i <ref>[https://www.ncbi.nlm.nih.gov/gene/672]</ref> [[Entrez]]Gene imaju referentne informacije za BRCA1 raka dojke 1, rani početak (Homo sapiens). [[Ortolozi]] ''BRCA1'' identificirani su u većini [[kičmenjak]]a za koje su dostupni kompletni podaci o [[genom]]u.<ref name="Ensembl"/>

== Struktura proteina ==
[[Protein]] BRCA1 sadrži sljedeće domene:<ref name="pmid9553742">{{cite journal | vauthors = Paterson JW | title = BRCA1: a review of structure and putative functions | journal = Dis. Markers | volume = 13 | issue = 4 | pages = 261–74 | date = februar 1998 | pmid = 9553742 | doi = 10.1155/1998/298530 | doi-access = free }}</ref>
* [[Cinkov prst]], tip C3HC4 ([[RING domenski prsten|RING-ov prst]])
* BRCA1 C Terminus ([[BRCT domain|BRCT]]) domain
Ovaj protein takođe sadrži motive [[signal jedarne lokalizacije|signala jedarne lokalizacije]] i signala jedarnog eksporta.<ref name="pmid16108063">{{cite journal | vauthors = Henderson BR | title = Regulation of BRCA1, BRCA2 and BARD1 intracellular trafficking | journal = BioEssays | volume = 27 | issue = 9 | pages = 884–93 | date = septembar 2005 | pmid = 16108063 | doi = 10.1002/bies.20277 | s2cid = 10138907 }}</ref>

Ljudski [[BRCA1 protein]] sastoji se od četiri glavna proteinska domena; [[RING-domenski prst|Znf C3HC4- RING domen]], domen BRCA1 i dva [[BRCT-domen|BRCT]] domena. Ovi domeni kodiraju približno 27% BRCA1 proteina. Poznato je šest izoformi BRCA1,<ref>UniProt Full|P38398|Breast cancer type 1 susceptibility protein}}</ref> sa [[izoforma]]ma 1 i 2 koje sadrže po 1.863 aminokiseline.

BRCA1 nije povezan sa [[BRCA2]], tj. oni nisu [[homologija sekvence|homolozi]] ili [[Paralog|paralozi]].<ref name="Irminger-Finger_2016"/>
[[slika:BRCA1partB.png|thumb|upright=2|alt=text|Mapa domena BRCA1; označeni su RING-domeni koji sadrže serin (SCD) i BRCT. Horizontalne crne linije označavaju domene koji vežu proteine za navedene partnere. Crveni krugovi označavaju mjesta fosforilacije.<ref name="pmid22737296">{{cite journal | vauthors = Clark SL, Rodriguez AM, Snyder RR, Hankins GD, Boehning D | title = Structure-Function Of The Tumor Suppressor BRCA1 | journal = Comput Struct Biotechnol J | volume = 1 | issue = 1 | pages = e201204005|date=april 2012 | pmid = 22737296 | pmc = 3380633 | doi = 10.5936/csbj.201204005 }}</ref>]]

== Funkcija i mehanizam ==

BRCA1 je dio kompleksa koji popravlja dvostruke niti u DNK. Lanci dvostruke zavojnice DNK neprekidno se lome jer se oštećuju. Ponekad je oštećen samo jedan polulanac, ponekad se oba prekidaju istovremeno. Sredstva za umrežavanje DNK važan su izvor oštećenja hromosoma/DNK. Dvolančane pukotine nastaju kao međuprodukti nakon uklanjanja umrežavanja i zaista su identificirane bialelne mutacije u '' BRCA1'', odgovorne za [[Fanconijeva anemija|Fanconijevu anemiju]], komplementacijsku skupinu S,<ref name="pmid25472942">{{cite journal |vauthors=Sawyer SL, Tian L, Kahkonen M, Schwartzentruber J, Kircher M, Majewski J, Dyment DA, Innes AM, Boycott KM, Moreau LA, Moilanen JS, Greenberg RA | title = Biallelic Mutations in BRCA1 Cause a New Fanconi Anemia Subtype | journal = Cancer Discov | volume = 5| issue = 2| pages = 135–42| year = 2014 | pmid = 25472942 | doi = 10.1158/2159-8290.CD-14-1156 | pmc=4320660}}</ref> genetiku bolest povezanu sa preosjetljivošću na agense za umrežavanje DNK. BRCA1 je dio proteinskog kompleksa koji popravlja DNK kad su oštećene obje niti. Kada se to dogodi, mehanizam za popravak teško može "znati" kako zamijeniti ispravnom sekvencom DNK, a postoji više načina za pokušaj popravka. Dvolančani mehanizam za popravak u kojem sudjeluje BRCA1 je [[homologmo usmjereni popravak]], gdje popravni proteini kopiraju identičnu sekvencu iz netaknute [[sestrinska hromatida|sestrinske hromatide]].<ref>{{Cite web |url=http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/D/DNArepair.html#DSBs |title=Kimball's Biologh Pages |access-date=23. 6. 2021 |archive-date=12. 2. 2018 |archive-url=https://web.archive.org/web/20180212073520/http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/D/DNArepair.html#DSBs |url-status=dead }}</ref>

U jedru mnogih tipova normalnih ćelija, protein BRCA1 tokom popravljanja dvonitnih preloma DNK komunicira sa [[RAD51]].<ref name="pmid17052168">{{cite journal | vauthors = Boulton SJ | title = Cellular functions of the BRCA tumour-suppressor proteins | journal = Biochem. Soc. Trans. | volume = 34 | issue = Pt 5 | pages = 633–45 | date = novembar 2006 | pmid = 17052168 | doi = 10.1042/BST0340633 }}</ref> Ti prekidi mogu biti uzrokovani prirodnim [[zračenje]]m ili drugim izlaganjem, ali se mogu dogoditi i kada [[hromosom]] razmijeni genetički materijal (homologna rekombinacija, npr."[[krosingover]]" tokom mejoze). Protein [[BRCA2]], koji ima funkciju sličnu funkciji BRCA1, također djeluje s proteinom RAD51. Utičući na sanaciju oštećenja DNK, ova tri proteina imaju ulogu u održavanju stabilnosti ljudskog genoma.

BRCA1 je također uključen u drugi tip popravke DNK, zvani [[DNK-mismač popravak|popravak neusklađenosti]]. BRCA1 stupa u interakciju s proteinom za popravak neusklađenosti DNK MSH2.<ref name="pmid11498787">{{cite journal | vauthors = Wang Q, Zhang H, Guerrette S, Chen J, Mazurek A, Wilson T, Slupianek A, Skorski T, Fishel R, Greene MI | title = Adenosine nucleotide modulates the physical interaction between hMSH2 and BRCA1 | journal = Oncogene | volume = 20 | issue = 34 | pages = 4640–9 | date = august 2001 | pmid = 11498787 | doi = 10.1038/sj.onc.1204625 | doi-access = free }}</ref> Objavljeno je da su MSH2, MSH6, PARP i neki drugi proteini koji su uključeni u popravak jednog lanca povišeni u tumorima dojke s nedostatkom BRCA1.<ref name="pmid22366898">{{cite journal | vauthors = Warmoes M, Jaspers JE, Pham TV, Piersma SR, Oudgenoeg G, Massink MP, Waisfisz Q, Rottenberg S, Boven E, Jonkers J, Jimenez CR | title = Proteomics of mouse BRCA1-deficient mammary tumors identifies DNA repair proteins with potential diagnostic and prognostic value in human breast cancer | journal = Mol. Cell. Proteomics | volume = 11 | issue = 7 | pages = M111.013334-1-M111.013334-19 | date = juli 2012 | pmid = 22366898 | pmc = 3394939 | doi = 10.1074/mcp.M111.013334 }}</ref>

Protein zvani [[valozin-sadržavajući protein]] (VCP, poznat i kao p97) ima ulogu u regrutaciji BRCA1 na oštećena mjesta DNK. Nakon ionizujućeg zračenja, VCP se regrutuje u lezije DNK i sudjeluje sa ubikvitin-ligazom RNF8, kako bi se orkestrirao sklop signalnih kompleksa za efikasnu popravku DSB.<ref name="pmid22020440">{{cite journal | vauthors = Meerang M, Ritz D, Paliwal S, Garajova Z, Bosshard M, Mailand N, Janscak P, Hübscher U, Meyer H, Ramadan K | title = The ubiquitin-selective segregase VCP/p97 orchestrates the response to DNA double-strand breaks | journal = Nat. Cell Biol. | volume = 13 | issue = 11 | pages = 1376–82 | date = novembar 2011 | pmid = 22020440 | doi = 10.1038/ncb2367 | s2cid = 22109822 }}</ref> BRCA1 komunicira sa VCP.<ref>{{cite journal | vauthors = Zhang H, Wang Q, Kajino K, Greene MI | title = VCP, a weak ATPase involved in multiple cellular events, interacts physically with BRCA1 in the nucleus of living cells | journal = DNA Cell Biol | volume = 19 | issue = 5 | pages = 253–263 | year = 2000 | pmid = 10855792 | doi = 10.1089/10445490050021168 }}</ref> BRCA1 također komunicira i s [[Myc|c-Myc]] i drugim proteinima koji su presudni za održavanje stabilnosti genoma.<ref name="pmid9788437">{{cite journal | vauthors = Wang Q, Zhang H, Kajino K, Greene MI | title = BRCA1 binds c-Myc and inhibits its transcriptional and transforming activity in cells | journal = Oncogene | volume = 17 | issue = 15 | pages = 1939–48 | date = oktobar 1998 | pmid = 9788437 | doi = 10.1038/sj.onc.1202403 | doi-access = free }}</ref>

BRCA1 se izravno veže za DNK, sa većim afinitetom za razgranate DNA strukture. Ova sposobnost vezanja za DNK doprinosi njenoj sposobnosti da inhibira aktivnost kompleksa [[nukleaza]] [[Mre11-Rad50-Nbs1|MRN]], kao i aktivnost same nukleaze Mre11.<ref name=Paull2001>{{cite journal | vauthors = Paull TT, Cortez D, Bowers B, Elledge SJ, Gellert M | title = Direct DNA binding by Brca1 | journal = Proceedings of the National Academy of Sciences | volume = 98 | issue = 11 | pages = 6086–6091 | year = 2001 | pmid = 11353843 | pmc = 33426 | doi = 10.1073/pnas.111125998 }}</ref> Ovo može objasniti ulogu BRCA1 u podsticanju popravka DNK manje vjernosti pomoću [[nehomologno spsjanje krajeva|nehomolognog spajanja krajeva]] (NHEJ).<ref name=Durant2005>{{cite journal | vauthors = Durant ST, Nickoloff JA | title = Good timing in the cell cycle for precise DNA repair by BRCA1 | journal = Cell Cycle | volume = 4 | issue = 9 | pages = 1216–22 | year = 2005 | pmid = 16103751 | doi = 10.4161/cc.4.9.2027 | doi-access = free }}</ref> BRCA1 se također kolokalizira sa γ-H2AX (histon H2AX fosforiliran na serinu-139) u žarištima popravljanja dvostrukih lanaca [[DNK]], što ukazuje da može imati ulogu u regrutovanju faktora popravka.<ref name=Starita2003/><ref name=Ye2001>{{cite journal | vauthors = Ye Q, Hu YF, Zhong H, Nye AC, Belmont AS, Li R | title = BRCA1-induced large-scale chromatin unfolding and allele-specific effects of cancer-predisposing mutations | journal = The Journal of Cell Biology | volume = 155 | issue = 6 | pages = 911–922 | year = 2001 | pmid = 11739404 | pmc = 2150890 | doi = 10.1083/jcb.200108049 }}</ref>

[[Formaldehid]] i [[acetaldehid]] uobičajeni su izvori poprečnih prekida DNK, često zahtijevajući popravke posredovane putem BRCA1, koji sadrži puteve.<ref name=Ridpath_2007>{{cite journal | vauthors = Ridpath JR, Nakamura A, Tano K, Luke AM, Sonoda E, Arakawa H, Buerstedde JM, Gillespie DA, Sale JE, Yamazoe M, Bishop DK, Takata M, Takeda S, Watanabe M, Swenberg JA, Nakamura J | title = Cells deficient in the FANC/BRCA pathway are hypersensitive to plasma levels of formaldehyde | journal = Cancer Res. | volume = 67 | issue = 23 | pages = 11117–22 | date = decembar 2007 | pmid = 18056434 | doi = 10.1158/0008-5472.CAN-07-3028 | doi-access = free }}</ref>

Ova funkcija popravljanja DNK je ključna; miševi sa mutacijama gubitka funkcije u oba BRCA1 [[alel]]a nisu održivi, a od 2015. godine poznato je da samo dvije odrasle osobe imaju takve mutacije; obje su imale urođene ili razvojne probleme, kao i [[kancer]]. Pretpostavljalo se da je jedna preživjela u odrasloj dobi, jer je jedna od mutacija BRCA1 bila [[hipomorf]]na.<ref>{{cite journal | vauthors = Prakash R, Zhang Y, Feng W, Jasin M | title = Homologous recombination and human health: the roles of BRCA1, BRCA2, and associated proteins | journal = Cold Spring Harbor Perspectives in Biology | volume = 7 | issue = 4 | pages = a016600 | date = april 2015 | pmid = 25833843 | pmc = 4382744 | doi = 10.1101/cshperspect.a016600 }}</ref>

=== Transkripcija ===

Pokazano je da BRCA1 ko-pročišćava s ljudskom [[RNK-polimeraza II|RNK-polimerazom II]], [[holoenzim]]om u ekstraktima [[HeLa]], implicirajući da je komponenta holoenzima.<ref name=Scully1997>{{cite journal | vauthors = Scully R, Anderson SF, Chao DM, Wei W, Ye L, Young RA, Livingston DM, Parvin JD | title = BRCA1 is a component of the RNA polymerase II holoenzyme | journal = Proceedings of the National Academy of Sciences | volume = 94 | issue = 11 | pages = 5605–10 | year = 1997 | pmid = 9159119 | pmc = 20825 | doi = 10.1073/pnas.94.11.5605 | bibcode = 1997PNAS...94.5605S }}</ref> Kasnija istraživanja, međutim, proturječila su ovoj pretpostavci, umjesto da su pokazala da je dominantni kompleks koji uključuje BRCA1 u HeLa ćelijama kompleks od dva megadaltona koji sadrži SWI/SNF.<ref name=Bochar2000>{{cite journal | vauthors = Bochar DA, Wang L, Beniya H, Kinev A, Xue Y, Lane WS, Wang W, Kashanchi F, Shiekhattar R | title = BRCA1 Is Associated with a Human SWI/SNF-Related Complex Linking Chromatin Remodeling to Breast Cancer | journal = Cell | volume = 102 | issue = 2 | pages = 257–265 | year = 2000 | pmid = 10943845 | doi = 10.1016/S0092-8674(00)00030-1 | doi-access = free }}</ref> SWI / SNF je kompleks za remodeliranje [[hromatin]]a. Pokazalo se da vještačko vezivanje BRCA1 za hromatin ne kondenzira heterokromatin, iako domen interakcije SWI / SNF nije bilo potreban za ovu ulogu.<ref name = Ye2001 /> BRCA1 stupa u interakciju s NELF-B ([[Kofaktor BRCA1|COBRA1]] ) podjedinica kompleksa [[Negativni faktor elongacije|NELF]].<ref name=Ye2001 /> BRCA1 je u interakciji sa NELF-B ([[Cofactor of BRCA1|COBRA1]]) podjedinicom [[Negative factor elongation|NELF]] kompleksa.<ref name=Ye2001 />

== Mutacije i rizik od raka ==
Određene varijacije gena ''BRCA1'' dovode do povećanog rizika za [[rak dojke|raka dojke]], kao dio [[nasljedni sindrom raka dojke-jajnika|nasljednog sindroma raka dojke-jajnika]]. Istraživači su identificirali stotine [[mutacija]] u genu '' BRCA1 '', od kojih su mnoge povezane s povećanim rizikom od raka. Žene s abnormalnim genom BRCA1 ili BRCA2 imaju do 80% rizika od razvoja raka dojke do 90. godine; povećani rizik od razvoja raka jajnika je oko 55% za žene s BRCA1 mutacijama i oko 25% za žene s mutacijama BRCA2.<ref name="urlGenetics">{{cite web | url = http://www.breastcancer.org/risk/factors/genetics | title = Genetics | date = 17. 9. 2012 | publisher = Breastcancer.org }}</ref>

Ove mutacije mogu biti promjene na jednom ili malom broju [[bazni par|baznih parova]] DNK (građevni blokovi DNK) i mogu se identificirati pomoću [[PCR]]-a i sekvenciranja DNK.

U nekim slučajevima se preuređuju veliki segmenti DNK. Ti veliki segmenti, koji se nazivaju i velikim rearanžmanima, mogu biti [[delecija (genetika)|delecija]] ili [[duplikacija (genetika)|duplikacija]] jednog ili nekoliko [[egzon]]a u genu. Klasični metodi za otkrivanje mutacija (sekvenciranje) nisu u stanju da otkriju ove tipove mutacija.<ref name="pmid15832305">{{cite journal | vauthors = Mazoyer S | title = Genomic rearrangements in the BRCA1 and BRCA2 genes | journal = Hum. Mutat. | volume = 25 | issue = 5 | pages = 415–22 | date = maj 2005 | pmid = 15832305 | doi = 10.1002/humu.20169 | s2cid = 32023181 }}</ref> Predloženi su i drugi metodi: standardna kvantitativna [[PCR]]-analiza,<ref name="pmid14984472">{{cite journal | vauthors = Barrois M, Bièche I, Mazoyer S, Champème MH, Bressac-de Paillerets B, Lidereau R | title = Real-time PCR-based gene dosage assay for detecting BRCA1 rearrangements in breast-ovarian cancer families | journal = Clin. Genet. | volume = 65 | issue = 2 | pages = 131–6 | date = februar 2004 | pmid = 14984472 | doi = 10.1111/j.0009-9163.2004.00200.x | s2cid = 11583160 }}</ref> [[MLPA|multipleks ligacijski-ovisne sonde]] (MLPA),<ref name="pmid12670888">{{cite journal | vauthors = Hogervorst FB, Nederlof PM, Gille JJ, McElgunn CJ, Grippeling M, Pruntel R, Regnerus R, van Welsem T, van Spaendonk R, Menko FH, Kluijt I, Dommering C, Verhoef S, Schouten JP, van't Veer LJ, Pals G | title = Large genomic deletions and duplications in the BRCA1 gene identified by a novel quantitative method | journal = Cancer Res. | volume = 63 | issue = 7 | pages = 1449–53 | date = april 2003 | pmid = 12670888 }}</ref> i kvantitativni multipleksni [[PCR]] kratkih fluorescentnih fragmenata (QMPSF).<ref name="pmid12203994">{{cite journal | vauthors = Casilli F, Di Rocco ZC, Gad S, Tournier I, Stoppa-Lyonnet D, Frebourg T, Tosi M | title = Rapid detection of novel BRCA1 rearrangements in high-risk breast-ovarian cancer families using multiplex PCR of short fluorescent fragments | journal = Hum. Mutat. | volume = 20 | issue = 3 | pages = 218–26 | date = septembar 2002 | pmid = 12203994 | doi = 10.1002/humu.10108 | s2cid = 24737909 }}</ref> Nedavno su predložene i novije metode: heterodupleksna analiza (HDA) multikapilarnom [[elektroforeza|elektroforezom]] ili također namjenskim sekvenciranjem [[oligonukleotid]]a, zasnovanom na [[uporedna genomska hibridizacija|upordnoj hibridizaciji genoma]] (mreža-CGH).<ref name="pmid17718857">{{cite journal | vauthors = Rouleau E, Lefol C, Tozlu S, Andrieu C, Guy C, Copigny F, Nogues C, Bieche I, Lidereau R | title = High-resolution oligonucleotide array-CGH applied to the detection and characterization of large rearrangements in the hereditary breast cancer gene BRCA1 | journal = Clin. Genet. | volume = 72 | issue = 3 | pages = 199–207 | date = septembar 2007 | pmid = 17718857 | doi = 10.1111/j.1399-0004.2007.00849.x | s2cid = 2393567 }}</ref>

Neki rezultati sugeriraju da bi se [[metilacija|hipermetilacija]] [[Promotor (genetika)|promotora]] BRCA1, koji je prijavljen kod nekih karcinoma, mogao smatrati mehanizmom za inaktivaciju ekspresije BRCA1.<ref name="pmid18567944">{{cite journal | vauthors = Tapia T, Smalley SV, Kohen P, Muñoz A, Solis LM, Corvalan A, Faundez P, Devoto L, Camus M, Alvarez M, Carvallo P | title = Promoter hypermethylation of BRCA1 correlates with absence of expression in hereditary breast cancer tumors | journal = Epigenetics | volume = 3 | issue = 1 | pages = 157–63 | year = 2008 | pmid = 18567944 | doi = 10.1186/bcr1858 | doi-access = free }}</ref>

Mutirani gen ''BRCA1'' obično stvara [[protein]] koji ne funkcionira pravilno. Vjeruje se da neispravni protein BRCA1 nije u stanju pomoći u popravljanju oštećenja DNK, što dovodi do mutacija drugih gena. Ove mutacije mogu se akumulirati i omogućiti ćelijama nekontrolirani rast i dijeljenje, kako bi stvorile tumor. Dakle, inaktivacijske mutacije BRCA1 dovode do predispozicije za rak.

BRCA1 [[iRNK]] [[tri primarna neprevedena područja|3'UTR]] može biti vezana za [[miRNK]], Mir-17 [[mikroRNK]]. Sugerira se da bi varijacije ove miRNA zajedno sa [[mikroRNK|Mir-30]] [[mikroRNK]] mogle izazvati osjetljivost na rak dojke.<ref>{{cite journal | vauthors = Shen J, Ambrosone CB, Zhao H | title = Novel genetic variants in microRNA genes and familial breast cancer | journal = Int. J. Cancer | volume = 124 | issue = 5 | pages = 1178–82 | date = mart 2009 | pmid = 19048628 | doi = 10.1002/ijc.24008 | doi-access = free }}</ref>

Pored karcinoma dojke, mutacije gena '' BRCA1 '' takođe povećavaju rizik od karcinoma [[rak jajnika|jajnika]] i [[rak prostate|prostate]]. Šta više, prekancerozne lezije ([[displazija]]) unutar [[jajovod]]a povezane su s mutacijama gena ''BRCA1''. Patogene mutacije bilo gdje u putevima modela koji sadrže BRCA1 i BRCA2 uveliko povećavaju rizike za podskupinu [[leukemija]] i limfoma.

Žene koje su naslijedile neispravan gen BRCA1 ili BRCA2 uveliko imaju povećan rizik od razvoja karcinoma dojke i jajnika. Njihov rizik od razvoja karcinoma dojke i/ili jajnika toliko je visok i toliko je specifičan za te karcinome da se mnogi nositelji mutacija odluče na profilaksnu operaciju. Bilo je mnogo nagađanja koja objašnjavaju tako očigledno zapanjujuću specifičnost tkiva. Glavne odrednice gdje se javljaju nasljedni karcinomi BRCA1/2 povezane su sa tkivnom specifičnošću patogena raka, agensa koji uzrokuje hroničnu upalu ili karcinogenezu. Ciljno tkivo može imati receptore za patogen, može biti selektivno izloženo upalnom procesu ili karcinogenu. Urođeni [[genom]]ski u nedostatak gena za supresiju tumora narušava normalne reakcije i pogoršava osjetljivost na bolesti u organima- metama. Ova teorija također uklapa podatke za nekoliko tumorskih supresora izvan BRCA1 ili BRCA2. Glavna prednost ovog modela je u tome što sugerira da se uz profilaksnu operaciju mogu obaviti i neke druge opcije.<ref name="Levin2012">{{cite journal | vauthors = Levin B, Lech D, Friedenson B | title = Evidence that BRCA1- or BRCA2-associated cancers are not inevitable | journal = Mol Med | volume = 18 | issue = 9 | pages = 1327–37 | year = 2012 | pmid = 22972572 | pmc = 3521784 | doi = 10.2119/molmed.2012.00280 }}</ref>

=== Mutacija '' BRCA1 '' u raku dojke i jajnika ===
Samo oko 3% –8% svih žena s rakom dojke ima mutaciju u BRCA1 ili BRCA2.<ref name="pmid9653432">{{cite journal |vauthors=Brody LC, Biesecker BB |title=Breast cancer susceptibility genes. BRCA1 and BRCA2 |journal=Medicine (Baltimore) |volume=77 |issue=3 |pages=208–26 |year=1998 |pmid=9653432 |doi= 10.1097/00005792-199805000-00006}}</ref> Slično tome, mutacije ''BRCA1'' nađene su samo kod oko 18% karcinoma jajnika (13% mutacija zametnih linija i 5% somatskih mutacija).<ref name="pmid24240112">{{cite journal |vauthors=Pennington KP, Walsh T, Harrell MI, Lee MK, Pennil CC, Rendi MH, Thornton A, Norquist BM, Casadei S, Nord AS, Agnew KJ, Pritchard CC, Scroggins S, Garcia RL, King MC, Swisher EM |title=Germline and somatic mutations in homologous recombination genes predict platinum response and survival in ovarian, fallopian tube, and peritoneal carcinomas |journal=Clin. Cancer Res. |volume=20 |issue=3 |pages=764–75 |year=2014 |pmid=24240112 |pmc=3944197 |doi=10.1158/1078-0432.CCR-13-2287 }}</ref>

Prema tome, dok je ekspresija BRCA1 kod većine ovih karcinoma niska, mutacija '' BRCA1 '' nije glavni uzrok smanjene ekspresije. Određeni latentni virusi, koji se često otkrivaju u tumorima raka dojke, mogu smanjiti ekspresiju gena BRCA1 i izazvati razvoj tumora dojke.<ref name="pmid30579323">{{cite journal | vauthors = Polansky H, Schwab H | title = How latent viruses cause breast cancer: An explanation based on the microcompetition model | journal = Bosnian Journal of Basic Medical Sciences | volume = 19 | issue = 3 | pages = 221–226 | date = august 2019 | pmid = 30579323 | pmc = 6716096 | doi = 10.17305/bjbms.2018.3950 }}</ref>

'''[[Karcinom dojke]] (uključujući i muški): Međuodnosi [[fenotip]] – [[genotip]]'''<ref>OMIM Entry Search - brca3</ref><ref>OMIM Entry - # 114480 - BREAST CANCER</ref><ref>https://omim.org/search?index=entry&sort=score+desc%2C+prefix_sort+desc&start=1&limit=10&search=brca3</ref>
{| class="wikitable" class="sortable wikitable" 
| bgcolor="lightblue" style="text-align:center;"|'''[[genski lokus|Lokacija]]'''
| bgcolor="khaki" style="text-align:center;"|'''[[Fenotip]]'''
| bgcolor="lightblue" style="text-align:center;"|'''Fenotipski MIM broj'''
| bgcolor="khaki" style="text-align:center;"|'''[[Nasljeđivanje]]'''<br>
+ oznaka mutacije
| bgcolor="lightblue" style="text-align:center;"|Ključ [[fenotip]]skog mapiranja
| bgcolor="khaki" style="text-align:center;"|Oznaka [[lokus (genetika)|lokusa]]
| bgcolor="lightblue" style="text-align:center;"|Genski/lokusni MIM broj
|- 
| style="text-align:center;"| 1p34.1 
| style="text-align:center;"|Invazivni duktusni
| style="text-align:center;"| 114480
| style="text-align:center;"|AD*, SMu
| style="text-align:center;"| 3
| style="text-align:center;"| RAD54L
| style="text-align:center;"| 603615
|-
| style="text-align:center;"| 2q33.1
| style="text-align:center;"|Zaštitni
| style="text-align:center;"| 114480
| style="text-align:center;"| AD, SMu
| style="text-align:center;"| 3
| style="text-align:center;"| CASP8
| style="text-align:center;"| 601763
|-
| style="text-align:center;"| 2q35
| style="text-align:center;"|Podložnost
| style="text-align:center;"| 114480
| style="text-align:center;"| AD, SMu
| style="text-align:center;"| 3
| style="text-align:center;"| BARD1
| style="text-align:center;"| 601593
|-
| style="text-align:center;"| 3q26.32
| style="text-align:center;"|Somatski
| style="text-align:center;"| 114480
| style="text-align:center;"| 
| style="text-align:center;"| 3
| style="text-align:center;"| PIK3CA
| style="text-align:center;"|171834
|-
| style="text-align:center;"| 5q34
| style="text-align:center;"|Podložnost
| style="text-align:center;"| 114480
| style="text-align:center;"| AD, SMu
| style="text-align:center;"| 3
| style="text-align:center;"| HMMR
| style="text-align:center;"| 600936
|-
| style="text-align:center;"| 6p25.2
| style="text-align:center;"|Podložnost (?)
| style="text-align:center;"| 114480
| style="text-align:center;"| AD, SMu
| style="text-align:center;"| 1
| style="text-align:center;"| NQO2
| style="text-align:center;"| 160998
|-
| style="text-align:center;"| 6q25 1-q25.2
| style="text-align:center;"|Somatski
| style="text-align:center;"| 114480
| style="text-align:center;"| 
| style="text-align:center;"| 3
| style="text-align:center;"| ESR1 
| style="text-align:center;"| 133430
|-
| style="text-align:center;"| 8q11.23
| style="text-align:center;"|Somatski
| style="text-align:center;"| 114480
| style="text-align:center;"| 
| style="text-align:center;"| 3
| style="text-align:center;"| RB1CC1
| style="text-align:center;"| 606837
|-
| style="text-align:center;"| 11p15.4 
| style="text-align:center;"|Somatski
| style="text-align:center;"| 114480
| style="text-align:center;"| 
| style="text-align:center;"| 3
| style="text-align:center;"| SLC22A1L
| style="text-align:center;"| 602631
|-
| style="text-align:center;"| 11q22.3 
| style="text-align:center;"|Podložnost
| style="text-align:center;"| 114480
| style="text-align:center;"| AD, SMu
| style="text-align:center;"| 3
| style="text-align:center;"| ATM
| style="text-align:center;"| 607585
|-
| style="text-align:center;"| 12p12.1 
| style="text-align:center;"|Somatski
| style="text-align:center;"| 114480
| style="text-align:center;"| 
| style="text-align:center;"| 3
| style="text-align:center;"| KRAS
| style="text-align:center;"| 190070
|-
| style="text-align:center;"| 13q13.1
| style="text-align:center;"|Podložnost, muški
| style="text-align:center;"| 114480
| style="text-align:center;"| AD, SMu
| style="text-align:center;"| 3
| style="text-align:center;"| [[BRCA2]]
| style="text-align:center;"| 600185
|-
| style="text-align:center;"| 14q32.33
| style="text-align:center;"|Podložnost
| style="text-align:center;"| 114480
| style="text-align:center;"| AD, SMu
| style="text-align:center;"| 3
| style="text-align:center;"| XRCC3
| style="text-align:center;"| 600675
|-
| style="text-align:center;"| 14q32.33
| style="text-align:center;"|Somatski
| style="text-align:center;"| 114480
| style="text-align:center;"| 
| style="text-align:center;"| 3
| style="text-align:center;"| AKT1
| style="text-align:center;"| 164730
|-
| style="text-align:center;"| 15q15.1
| style="text-align:center;"|Podložnost
| style="text-align:center;"| 114480
| style="text-align:center;"| AD, SMu
| style="text-align:center;"| 3
| style="text-align:center;"| RAD51
| style="text-align:center;"| 179617
|-
| style="text-align:center;"| 16p12.2 
| style="text-align:center;"|Podložnost
| style="text-align:center;"| 114480
| style="text-align:center;"| AD, SMu
| style="text-align:center;"| 3
| style="text-align:center;"| PALB2
| style="text-align:center;"| 610355
|-
| style="text-align:center;"| 16q22.1
| style="text-align:center;"|Režanjski
| style="text-align:center;"| 114480
| style="text-align:center;"| AD, SMu
| style="text-align:center;"| 3
| style="text-align:center;"| CDH1
| style="text-align:center;"| 192090
|-
| style="text-align:center;"| 17q21.33
| style="text-align:center;"|Podložnost
| style="text-align:center;"| 114480
| style="text-align:center;"| AD, SMu
| style="text-align:center;"| 3
| style="text-align:center;"| PHB
| style="text-align:center;"| 176705
|-
| style="text-align:center;"| 17p13.1
| style="text-align:center;"|Somatski
| style="text-align:center;"| 114480
| style="text-align:center;"| 
| style="text-align:center;"| 3
| style="text-align:center;"| TP53
| style="text-align:center;"| 191170
|-
| style="text-align:center;"| 17q23.2
| style="text-align:center;"|Somatski
| style="text-align:center;"| 114480
| style="text-align:center;"|
| style="text-align:center;"| 3
| style="text-align:center;"| PPM1D
| style="text-align:center;"| 605100
|-
| style="text-align:center;"| 17q23.2
| style="text-align:center;"|Ranopojavna podložnost
| style="text-align:center;"| 114480
| style="text-align:center;"| AD, SMu
| style="text-align:center;"| 3
| style="text-align:center;"| BRIP1
| style="text-align:center;"| 605882
|-
| style="text-align:center;"| 22q12.1
| style="text-align:center;"|Podložnost
| style="text-align:center;"| 114480
| style="text-align:center;"| AD, SMu
| style="text-align:center;"| 3
| style="text-align:center;"| CHEK2
| style="text-align:center;"| 604373
|-
|}
*'''AD''' = [[autosomno nasljeđivanje|Autosomno dominantno nasljeđivanje]]

=== Promotorska hipermetilacija ''BRCA1'' u raku dojke i jajnika ===
[[DNK metilacija|Promotorska hipermetilacija]] ''BRCA1'' bila je prisutan u samo 13% neizabranih primarnih karcinoma dojke.<ref name="pmid10749912">{{cite journal |vauthors=Esteller M, Silva JM, Dominguez G, Bonilla F, Matias-Guiu X, Lerma E, Bussaglia E, Prat J, Harkes IC, Repasky EA, Gabrielson E, Schutte M, Baylin SB, Herman JG |author-link13=Stephen B. Baylin |author-link14=James G. Herman |title=Promoter hypermethylation and BRCA1 inactivation in sporadic breast and ovarian tumors |journal=J. Natl. Cancer Inst. |volume=92 |issue=7 |pages=564–9 |year=2000 |pmid=10749912 |doi= 10.1093/jnci/92.7.564|doi-access=free }}</ref> Slično tome, hipermetilacija promotora ''BRCA1'' bila je prisutna u samo 5% do 15% slučajeva EOC-a.

Dakle, dok je ekspresija BRCA1 kod ovih karcinoma niska, metilacija promotora ''BRCA1'' samo je manji uzrok smanjene ekspresije.

=== MikroRNK represija ''BRCA1'' kod karcinoma dojke ===
Postoji niz specifičnih [[mikroRNK]], , koje, kada su prekomerno eksprimirane, direktno smanjuju ekspresiju specifičnih proteina koji popravljaju DNK (vidi [[mikroRNK]], odjeljak: [[popravak DNK]] i rak). U slučaju raka dojke, mikroRNK-182 (miR-182) specifično cilja BRCA1.<ref name=Moskwa>{{cite journal |vauthors=Moskwa P, Buffa FM, Pan Y, Panchakshari R, Gottipati P, Muschel RJ, Beech J, Kulshrestha R, Abdelmohsen K, Weinstock DM, Gorospe M, Harris AL, Helleday T, Chowdhury D |title=miR-182-mediated downregulation of BRCA1 impacts DNA repair and sensitivity to PARP inhibitors |journal=Mol. Cell |volume=41 |issue=2 |pages=210–20 |year=2011 |pmid=21195000 |pmc=3249932 |doi=10.1016/j.molcel.2010.12.005 }}</ref> Rak dojke može se klasificirati na osnovu statusa receptora ili histoloških obilježja, u [[trostruko negativni rak dojke]] (15% –25% karcinoma dojke), [[rak dojke|HER2 +]] (15% –30% karcinoma dojke), [[Estrogeni receptor|ER +]] / [[Progesteronski receptor|PR +]] (oko 70% karcinoma dojke) i [[Invazivni režanjski karcinom]] (oko 5% –10% invazivnog karcinoma dojke). Utvrđeno je da sva četiri tipa karcinoma dojke u prosjeku imaju oko 100 puta veći porast miR-182 u odnosu na normalno tkivo dojke.<ref name="pmid23249749">{{cite journal |vauthors=Krishnan K, Steptoe AL, Martin HC, Wani S, Nones K, Waddell N, Mariasegaram M, Simpson PT, Lakhani SR, Gabrielli B, Vlassov A, Cloonan N, Grimmond SM |title=MicroRNA-182-5p targets a network of genes involved in DNA repair |journal=RNA |volume=19 |issue=2 |pages=230–42 |year=2013 |pmid=23249749 |pmc=3543090 |doi=10.1261/rna.034926.112 }}</ref> U ćelijskim linijama karcinoma dojke postoji inverzna korelacija nivoa proteina BRCA1 sa ekspresijom miR-182. Stoga se čini da je velik dio smanjenja ili odsustva BRCA1 kod duktusnih karcinoma dojke visokog stepena prekomjerno eksprimirani miR-182.

Pored miR-182, par gotovo identičnih [[mikroRNK]], miR-146a i miR-146b-5p, također potiskuju ekspresiju BRCA1. Ove dvije mikroRNK su prekomjerno eksprimirane u trostruko negativnim tumorima i njihova prekomjerna ekspresija rezultira inaktivacijom BRCA1. Dakle, miR-146a i / ili miR-146b-5p mogu također doprinijeti smanjenoj ekspresiji BRCA1 kod ovih trostruko negativnih karcinoma dojke.

=== MikroRNK represija ''BRCA1'' kod karcinoma jajnika ===
I u [[Rak jajnika|seroznim tubulskim intraepitelnim karcinomima]] (prethodnica lezije [[Rak jajnika|visokoeksprimiranog seroznog karcinoma jajnika (HG-SOC)]]), i u samom HG-SOC, miR- 182 je prekomjerno eksprimiran u oko 70% slučajeva.<ref name="pmid21472990">{{cite journal |vauthors=Garcia AI, Buisson M, Bertrand P, Rimokh R, Rouleau E, Lopez BS, Lidereau R, Mikaélian I, Mazoyer S |title=Down-regulation of BRCA1 expression by miR-146a and miR-146b-5p in triple negative sporadic breast cancers |journal=EMBO Mol Med |volume=3 |issue=5 |pages=279–90 |year=2011 |pmid=21472990 |pmc=3377076 |doi=10.1002/emmm.201100136 }}</ref> Dakle, miR-146a i / ili miR-146b-5p mogu takođe doprinijeti smanjenoj ekspresiji BRCA1 kod ovih trostruko negativnih karcinoma dojke.

Još jedna mikroRNK za koju je poznato da smanjuje ekspresiju BRCA1 u ćelijamama raka jajnika je miR-9. Među 58 tumora pacijenata sa stadijem IIIC ili stadijem IV seroznog karcinoma jajnika (HG-SOG), pronađena je inverzna korelacija između ekspresija miR-9 i BRCA1, tako da povećani miR-9 kod ovih karcinoma jajnika također može doprinijeti smanjenoj ekspresiji BRCA1.

=== Nedostatak ekspresije '' BRCA1'' – vjerovatno tumorogen ===

Oštećenje DNK je primarni uzrok raka,<ref name="pmid18403632">{{cite journal |vauthors=Kastan MB |title=DNA damage responses: mechanisms and roles in human disease: 2007 G.H.A. Clowes Memorial Award Lecture |journal=Mol. Cancer Res. |volume=6 |issue=4 |pages=517–24 |year=2008 |pmid=18403632 |doi=10.1158/1541-7786.MCR-08-0020 |doi-access=free }}</ref> a izgleda da su nedostaci u popravljanju DNK u osnovi mnogih oblika raka.<ref name="pmid18082599">{{cite journal |vauthors=Harper JW, Elledge SJ |title=The DNA damage response: ten years after |journal=Mol. Cell |volume=28 |issue=5 |pages=739–45 |year=2007 |pmid=18082599 |doi=10.1016/j.molcel.2007.11.015 |doi-access=free }}</ref> Ako je [[popravak DNK]] nedostatan, oštećenje DNK se akumulira. Takav višak oštećenja DNK može povećati [[mutacija|mutacijske]] greške tokom [[replikacija DNK|replikacije]] zbog sklonosti greškama [[popravak DNK|sintezi translezije]]. Prekomjerna oštećenja DNK mogu također povećati [[Epigenetika|epigenetičke]] promjene, zbog grešaka tokom popravka DNK.<ref name=Hagan>{{cite journal | vauthors = O'Hagan HM, Mohammad HP, Baylin SB | title = Double strand breaks can initiate gene silencing and SIRT1-dependent onset of DNA methylation in an exogenous promoter CpG island | journal = PLOS Genetics | volume = 4 | issue = 8 | pages = e1000155 | year = 2008 | pmid = 18704159 | pmc = 2491723 | doi = 10.1371/journal.pgen.1000155 }}</ref><ref name=Cuozzo>{{cite journal | vauthors = Cuozzo C, Porcellini A, Angrisano T, Morano A, Lee B, Di Pardo A, Messina S, Iuliano R, Fusco A, Santillo MR, Muller MT, Chiariotti L, Gottesman ME, Avvedimento EV | title = DNA damage, homology-directed repair, and DNA methylation | journal = PLOS Genetics | volume = 3 | issue = 7 | pages = e110 | date = Jul 2007 | pmid = 17616978 | pmc = 1913100 | doi = 10.1371/journal.pgen.0030110 }}</ref> Takve mutacije i epigenetičke promjene mogu dovesti do [[karcinom]]a. Česti nedostatak '' BRCA1 '' izazvan mikroRNK kod karcinoma dojke i jajnika vjerovatno pridonosi njihovom napredovanju.

{| class="wikitable"
|-
! Populacija ili podrrupa !!Mutacija BRCA1<ref name="denDunnen2000">{{cite journal | vauthors = den Dunnen JT, Antonarakis SE | title = Mutation nomenclature extensions and suggestions to describe complex mutations: a discussion | journal = Human Mutation | volume = 15 | issue = 1 | pages = 7–12 | year = 2000 | pmid = 10612815 | doi = 10.1002/(SICI)1098-1004(200001)15:1<7::AID-HUMU4>3.0.CO;2-N | doi-access = free }}</ref>!! Reference
|-
| Afroamerikanci || 943ins10, M1775R || <ref name="Neuhausen2000">{{cite journal | vauthors = Neuhausen SL | title = Founder populations and their uses for breast cancer genetics | journal = Cancer Research | volume = 2 | issue = 2 | pages = 77–81 | year = 2000 | pmid = 11250694 | pmc = 139426 | doi = 10.1186/bcr36 }}</ref>
|-
| Afrikanci || E881X, 1374delC || <ref name="Reeves2004">{{cite journal | vauthors = Reeves MD, Yawitch TM, van der Merwe NC, van den Berg HJ, Dreyer G, van Rensburg EJ | title = BRCA1 mutations in South African breast and/or ovarian cancer families: evidence of a novel founder mutation in Afrikaner families | journal = Int. J. Cancer | volume = 110 | issue = 5 | pages = 677–82 | date = juli 2004 | pmid = 15146556 | doi = 10.1002/ijc.20186 | s2cid = 22970255 | doi-access = free }}</ref><ref name="Francies2015">{{cite journal | vauthors = Francies FZ, Wainstein T, De Leeneer K, Cairns A, Murdoch M, Nietz S, Cubasch H, Poppe B, Van Maerken T, Crombez B, Coene I, Kerr R, Slabbert JP, Vral A, Krause A, Baeyens A | title = BRCA1, BRCA2 and PALB2 mutations and CHEK2 c.1100delC in different South African ethnic groups diagnosed with premenopausal and/or triple negative breast cancer | journal = BMC Cancer | volume = 15 | pages = 912 | date = Nov 2015 | pmid = 26577449 | doi = 10.1186/s12885-015-1913-6 | doi-access = free | pmc=4647511}}</ref>
|-
| Aškenazi Jevreji || 185delAG, 188del11, 5382insC ||<ref name="Tonin1995">{{cite journal | vauthors = Tonin P, Serova O, Lenoir G, Lynch H, Durocher F, Simard J, Morgan K, Narod S | title = BRCA1 mutations in Ashkenazi Jewish women | journal = American Journal of Human Genetics | volume = 57 | issue = 1 | page = 189 | year = 1995 | pmid = 7611288 | pmc = 1801236 }}</ref><ref name="Narod2004">{{cite journal | vauthors = Narod SA, Foulkes WD | title = BRCA1 and BRCA2: 1994 and beyond | journal = Nature Reviews Cancer | volume = 4 | issue = 9 | pages = 665–676 | year = 2004 | pmid = 15343273 | doi = 10.1038/nrc1431 | s2cid = 30686068 }}</ref> 
|-
| Austrijanci || 2795delA, C61G, 5382insC, Q1806stop || <ref name="Wagner1998">{{cite journal | vauthors = Wagner TM, Möslinger RA, Muhr D, Langbauer G, Hirtenlehner K, Concin H, Doeller W, Haid A, Lang AH, Mayer P, Ropp E, Kubista E, Amirimani B, Helbich T, Becherer A, Scheiner O, Breiteneder H, Borg A, Devilee P, Oefner P, Zielinski C | title = BRCA1-related breast cancer in Austrian breast and ovarian cancer families: specific BRCA1 mutations and pathological characteristics | journal = International Journal of Cancer | volume = 77 | issue = 3 | pages = 354–360 | year = 1998 | pmid = 9663595 | doi = 10.1002/(SICI)1097-0215(19980729)77:3<354::AID-IJC8>3.0.CO;2-N | doi-access = free }}</ref>
|-
| Belgijanci || 2804delAA, IVS5+3A>G || <ref name="Peelen1997">{{cite journal | vauthors = Peelen T, van Vliet M, Petrij-Bosch A, Mieremet R, Szabo C, van den Ouweland AM, Hogervorst F, Brohet R, Ligtenberg MJ, Teugels E, van der Luijt R, van der Hout AH, Gille JJ, Pals G, Jedema I, Olmer R, van Leeuwen I, Newman B, Plandsoen M, van der Est M, Brink G, Hageman S, Arts PJ, Bakker MM, Devilee P | title = A high proportion of novel mutations in BRCA1 with strong founder effects among Dutch and Belgian hereditary breast and ovarian cancer families | journal = American Journal of Human Genetics | volume = 60 | issue = 5 | pages = 1041–1049 | year = 1997 | pmid = 9150151 | pmc = 1712432 }}</ref><ref name="Claes1999">{{cite journal | vauthors = Claes K, Machackova E, De Vos M, Poppe B, De Paepe A, Messiaen L | title = Mutation analysis of the BRCA1 and BRCA2 genes in the Belgian patient population and identification of a Belgian founder mutation BRCA1 IVS5 + 3A > G | journal = Disease Markers | volume = 15 | issue = 1–3 | pages = 69–73 | year = 1999 | pmid = 10595255 | pmc = 3851655 | doi = 10.1155/1999/241046 }}</ref>
|-
| Nizozemci || Delecija egzona 2, delecija egzona 3, 2804delAA || <ref name="Peelen1997"/><ref name="PetrijBosch">{{cite journal | vauthors = Petrij-Bosch A, Peelen T, van Vliet M, van Eijk R, Olmer R, Drüsedau M, Hogervorst FB, Hageman S, Arts PJ, Ligtenberg MJ, Meijers-Heijboer H, Klijn JG, Vasen HF, Cornelisse CJ, van 't Veer LJ, Bakker E, van Ommen GJ, Devilee P | title = BRCA1 genomic deletions are major founder mutations in Dutch breast cancer patients | journal = Nature Genetics | volume = 17 | issue = 3 | pages = 341–345 | year = 1997 | pmid = 9354803 | doi = 10.1038/ng1197-341 | hdl = 1765/54808 | s2cid = 13028232 | url = https://repub.eur.nl/pub/54808/ng1197-341.pdf }}</ref><ref name="Verhoog">{{cite journal | vauthors = Verhoog LC, van den Ouweland AM, Berns E, van Veghel-Plandsoen MM, van Staveren IL, Wagner A, Bartels CC, Tilanus-Linthorst MM, Devilee P, Seynaeve C, Halley DJ, Niermeijer MF, Klijn JG, Meijers-Heijboer H | title = Large regional differences in the frequency of distinct BRCA1/BRCA2 mutations in 517 Dutch breast and/or ovarian cancer families | journal = European Journal of Cancer | volume = 37 | issue = 16 | pages = 2082–2090 | year = 2001 | pmid = 11597388 | doi = 10.1016/S0959-8049(01)00244-1 }}</ref>
|-
| Finci|| 3745delT, IVS11-2A>G || <ref name="Huusko">{{cite journal | vauthors = Huusko P, Pääkkönen K, Launonen V, Pöyhönen M, Blanco G, Kauppila A, Puistola U, Kiviniemi H, Kujala M, Leisti J, Winqvist R | title = Evidence of founder mutations in Finnish BRCA1 and BRCA2 families | journal = American Journal of Human Genetics | volume = 62 | issue = 6 | pages = 1544–1548 | year = 1998 | pmid = 9585608 | pmc = 1377159 | doi = 10.1086/301880 }}</ref><ref name="Paakkonen">{{cite journal | vauthors = Pääkkönen K, Sauramo S, Sarantaus L, Vahteristo P, Hartikainen A, Vehmanen P, Ignatius J, Ollikainen V, Kääriäinen H, Vauramo E, Nevanlinna H, Krahe R, Holli K, Kere J | title = Involvement of BRCA1 and BRCA2 in breast cancer in a western Finnish sub-population | journal = Genetic Epidemiology | volume = 20 | issue = 2 | pages = 239–246 | year = 2001 | pmid = 11180449 | doi = 10.1002/1098-2272(200102)20:2<239::AID-GEPI6>3.0.CO;2-Y }}</ref>
|-
| Francuzi || 3600del11, G1710X || <ref name="Muller">{{cite journal | vauthors = Muller D, Bonaiti-Pellié C, Abecassis J, Stoppa-Lyonnet D, Fricker JP | title = BRCA1 testing in breast and/or ovarian cancer families from northeastern France identifies two common mutations with a founder effect | journal = Familial Cancer | volume = 3 | issue = 1 | pages = 15–20 | year = 2004 | pmid = 15131401 | doi = 10.1023/B:FAME.0000026819.44213.df | s2cid = 24615109 }}</ref>
|-
| Francuski Kanađani || C4446T || <ref name="Tonin1999">{{cite journal | vauthors = Tonin PN, Mes-Masson AM, Narod SA, Ghadirian P, Provencher D | title = Founder BRCA1 and BRCA2 mutations in French Canadian ovarian cancer cases unselected for family history | journal = Clinical Genetics | volume = 55 | issue = 5 | pages = 318–324 | year = 1999 | pmid = 10422801 | doi = 10.1034/j.1399-0004.1999.550504.x | s2cid = 23931343 }}</ref>
|-
| Nijemci|| 5382insC, 4184del4 || <ref name="Backe1999">{{cite journal | vauthors = Backe J, Hofferbert S, Skawran B, Dörk T, Stuhrmann M, Karstens JH, Untch M, Meindl A, Burgemeister R, Chang-Claude J, Weber BH | title = Frequency of BRCA1 mutation 5382insC in German breast cancer patients | journal = Gynecologic Oncology | volume = 72 | issue = 3 | pages = 402–406 | year = 1999 | pmid = 10053113 | doi = 10.1006/gyno.1998.5270 }}</ref><ref name="urlBrca1">{{cite web | url = http://mutview.dmb.med.keio.ac.jp/MutationView/jsp/mutview/html/brca1.html | title = Mutation data of the BRCA1 gene | work = KMDB/MutationView (Keio Mutation Databases) | publisher = Keio University }}</ref>
|-
| Grci|| 5382insC || <ref name="Ladopoulou2002">{{cite journal | vauthors = Ladopoulou A, Kroupis C, Konstantopoulou I, Ioannidou-Mouzaka L, Schofield AC, Pantazidis A, Armaou S, Tsiagas I, Lianidou E, Efstathiou E, Tsionou C, Panopoulos C, Mihalatos M, Nasioulas G, Skarlos D, Haites NE, Fountzilas G, Pandis N, Yannoukakos D | title = Germ line BRCA1 and BRCA2 mutations in Greek breast/ovarian cancer families: 5382insC is the most frequent mutation observed | journal = Cancer Letters | volume = 185 | issue = 1 | pages = 61–70 | year = 2002 | pmid = 12142080 | doi = 10.1016/S0304-3835(01)00845-X }}</ref>
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| Mađari || 300T>G, 5382insC, 185delAG || <ref name="VanDerLooij2000">{{cite journal | vauthors = Van Der Looij M, Szabo C, Besznyak I, Liszka G, Csokay B, Pulay T, Toth J, Devilee P, King MC, Olah E | title = Prevalence of founder BRCA1 and BRCA2 mutations among breast and ovarian cancer patients in Hungary | journal = International Journal of Cancer | volume = 86 | issue = 5 | pages = 737–740 | year = 2000 | pmid = 10797299 | doi = 10.1002/(SICI)1097-0215(20000601)86:5<737::AID-IJC21>3.0.CO;2-1 }}</ref>
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| Italijani || 5083del19 || <ref name="Baudi2001">{{cite journal | vauthors = Baudi F, Quaresima B, Grandinetti C, Cuda G, Faniello C, Tassone P, Barbieri V, Bisegna R, Ricevuto E, Conforti S, Viel A, Marchetti P, Ficorella C, Radice P, Costanzo F, Venuta S | title = Evidence of a founder mutation of BRCA1 in a highly homogeneous population from southern Italy with breast/ovarian cancer | journal = Human Mutation | volume = 18 | issue = 2 | pages = 163–164 | year = 2001 | pmid = 11462242 | doi = 10.1002/humu.1167 | s2cid = 2995 | doi-access = free }}</ref>
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| Japanci|| L63X, Q934X || <ref name="Sekine2001">{{cite journal | vauthors = Sekine M, Nagata H, Tsuji S, Hirai Y, Fujimoto S, Hatae M, Kobayashi I, Fujii T, Nagata I, Ushijima K, Obata K, Suzuki M, Yoshinaga M, Umesaki N, Satoh S, Enomoto T, Motoyama S, Tanaka K | title = Mutational analysis of BRCA1 and BRCA2 and clinicopathologic analysis of ovarian cancer in 82 ovarian cancer families: two common founder mutations of BRCA1 in Japanese population | journal = Clinical Cancer Research | volume = 7 | issue = 10 | pages = 3144–3150 | year = 2001 | pmid = 11595708 }}</ref>
|-
| Autohtoni Amerikanci || 1510insG, 1506A>G || <ref name="Liede2002b">{{cite journal | vauthors = Liede A, Jack E, Hegele RA, Narod SA | title = A BRCA1 mutation in Native North American families | journal = Human Mutation | volume = 19 | issue = 4 | page = 460 | year = 2002 | pmid = 11933205 | doi = 10.1002/humu.9027 | s2cid = 37710898 | doi-access = free }}</ref>
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| Sjeverni Irci || 2800delAA || <ref name="TSNI2003">{{cite journal |author=The Scottish/Northern Irish BRCA1/BRCA2 Consortium | title = BRCA1 and BRCA2 mutations in Scotland and Northern Ireland | journal = British Journal of Cancer | volume = 88 | issue = 8 | pages = 1256–1262 | year = 2003 | pmid = 12698193 | pmc = 2747571 | doi = 10.1038/sj.bjc.6600840 }}</ref>
|-
| Norvežani|| 816delGT, 1135insA, 1675delA, 3347delAG || <ref name="Borg1999">{{cite journal | vauthors = Borg A, Dørum A, Heimdal K, Maehle L, Hovig E, Møller P | title = BRCA1 1675delA and 1135insA account for one third of Norwegian familial breast-ovarian cancer and are associated with later disease onset than less frequent mutations | journal = Disease Markers | volume = 15 | issue = 1–3 | pages = 79–84 | year = 1999 | pmid = 10595257 | pmc = 3851406 | doi = 10.1155/1999/278269 }}</ref><ref name="Heimdal2003">{{cite journal | vauthors = Heimdal K, Maehle L, Apold J, Pedersen JC, Møller P | title = The Norwegian founder mutations in BRCA1: high penetrance confirmed in an incident cancer series and differences observed in the risk of ovarian cancer | journal = European Journal of Cancer | volume = 39 | issue = 15 | pages = 2205–2213 | year = 2003 | pmid = 14522380 | doi = 10.1016/S0959-8049(03)00548-3 }}</ref>
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| Pakistanci || 2080insA, 3889delAG, 4184del4, 4284delAG, IVS14-1A>G || <ref name="Liede2002">{{cite journal | vauthors = Liede A, Malik IA, Aziz Z, Rios Pd Pde L, Kwan E, Narod SA | title = Contribution of BRCA1 and BRCA2 Mutations to Breast and Ovarian Cancer in Pakistan | journal = American Journal of Human Genetics | volume = 71 | issue = 3 | pages = 595–606 | year = 2002 | pmid = 12181777 | pmc = 379195 | doi = 10.1086/342506 }}</ref>
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| Poljaci|| 300T>G, 5382insC, C61G, 4153delA || <ref name="Gorski2000">{{cite journal | vauthors = Górski B, Byrski T, Huzarski T, Jakubowska A, Menkiszak J, Gronwald J, Pluzańska A, Bebenek M, Fischer-Maliszewska L, Grzybowska E, Narod SA, Lubiński J | title = Founder mutations in the BRCA1 gene in Polish families with breast-ovarian cancer | journal = American Journal of Human Genetics | volume = 66 | issue = 6 | pages = 1963–1968 | year = 2000 | pmid = 10788334 | pmc = 1378051 | doi = 10.1086/302922 }}</ref><ref name="Perkowska2003">{{cite journal | vauthors = Perkowska M, BroZek I, Wysocka B, Haraldsson K, Sandberg T, Johansson U, Sellberg G, Borg A, Limon J | title = BRCA1 and BRCA2 mutation analysis in breast-ovarian cancer families from northeastern Poland | journal = Hum. Mutat. | volume = 21 | issue = 5 | pages = 553–4 | date = maj 2003 | pmid = 12673801 | doi = 10.1002/humu.9139 | s2cid = 7001156 | doi-access = free }}</ref>
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| Rusi || 5382insC, 4153delA || <ref name="Gayther1997">{{cite journal | vauthors = Gayther SA, Harrington P, Russell P, Kharkevich G, Garkavtseva RF, Ponder BA | title = Frequently occurring germ-line mutations of the BRCA1 gene in ovarian cancer families from Russia | journal = Am. J. Hum. Genet. | volume = 60 | issue = 5 | pages = 1239–42 | date = maj 1997 | pmid = 9150173 | pmc = 1712436 }}</ref>
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| Škoti || 2800delAA || <ref name="TSNI2003"/><ref name="Liede2000">{{cite journal | vauthors = Liede A, Cohen B, Black DM, Davidson RH, Renwick A, Hoodfar E, Olopade OI, Micek M, Anderson V, De Mey R, Fordyce A, Warner E, Dann JL, King MC, Weber B, Narod SA, Steel CM | title = Evidence of a founder BRCA1 mutation in Scotland | journal = Br. J. Cancer | volume = 82 | issue = 3 | pages = 705–11 | date = februar 2000 | pmid = 10682686 | pmc = 2363321 | doi = 10.1054/bjoc.1999.0984 }}</ref>
|-
| Španci || R71G || <ref name="Vega2001">{{cite journal | vauthors = Vega A, Campos B, Bressac-De-Paillerets B, Bond PM, Janin N, Douglas FS, Domènech M, Baena M, Pericay C, Alonso C, Carracedo A, Baiget M, Diez O | title = The R71G BRCA1 is a founder Spanish mutation and leads to aberrant splicing of the transcript | journal = Hum. Mutat. | volume = 17 | issue = 6 | pages = 520–1 | date = juni 2001 | pmid = 11385711 | doi = 10.1002/humu.1136 | s2cid = 39462456 | doi-access = free }}</ref><ref name="Campos2003">{{cite journal | vauthors = Campos B, Díez O, Odefrey F, Domènech M, Moncoutier V, Martínez-Ferrandis JI, Osorio A, Balmaña J, Barroso A, Armengod ME, Benítez J, Alonso C, Stoppa-Lyonnet D, Goldgar D, Baiget M | title = Haplotype analysis of the BRCA2 9254delATCAT recurrent mutation in breast/ovarian cancer families from Spain | journal = Hum. Mutat. | volume = 21 | issue = 4 | page = 452 | date = april 2003 | pmid = 12655574 | doi = 10.1002/humu.9133 | s2cid = 34333797 | doi-access = free }}</ref>
|-
| Šveđani || Q563X, 3171ins5, 1201del11, 2594delC || <ref name="Neuhausen2000"/><ref name="Bergman2001">{{cite journal | vauthors = Bergman A, Einbeigi Z, Olofsson U, Taib Z, Wallgren A, Karlsson P, Wahlström J, Martinsson T, Nordling M | title = The western Swedish BRCA1 founder mutation 3171ins5; a 3.7 cM conserved haplotype of today is a reminiscence of a 1500-year-old mutation | journal = Eur. J. Hum. Genet. | volume = 9 | issue = 10 | pages = 787–93 | date = oktobar 2001 | pmid = 11781691 | doi = 10.1038/sj.ejhg.5200704 | doi-access = free }}</ref>
|}

== Hemoterapija kancera ==
[[NSCLC|Nemaloćelijski rak pluća]] (NSCLC) vodeći je uzrok smrti od raka u svijetu. Pri dijagnozi, gotovo 70% osoba s NSCLC ima lokalno uznapredovalu ili metastatsku bolest. Osobe s NSCLC često se liječe terapijskim spojevima platine (npr. cisplatinom, karboplatinom ili oksaliplatinom) koji uzrokuju međulančane unakrsne veze u DNK. Među osobama s NSCLC, niska ekspresija '' BRCA1 '' u primarnom tumoru korelirala je s poboljšanim preživljavanjem nakon hemoterapije koja sadrži platinu.<ref name=Taron>{{cite journal | vauthors = Taron M, Rosell R, Felip E, Mendez P, Souglakos J, Ronco MS, Queralt C, Majo J, Sanchez JM, Sanchez JJ, Maestre J | title = BRCA1 mRNA expression levels as an indicator of chemoresistance in lung cancer | journal = Hum. Mol. Genet. | volume = 13 | issue = 20 | pages = 2443–9 | date = oktobar 2004 | pmid = 15317748 | doi = 10.1093/hmg/ddh260 | doi-access = free }}</ref><ref name=Papadaki>{{cite journal | vauthors = Papadaki C, Sfakianaki M, Ioannidis G, Lagoudaki E, Trypaki M, Tryfonidis K, Mavroudis D, Stathopoulos E, Georgoulias V, Souglakos J | title = ERCC1 and BRAC1 mRNA expression levels in the primary tumor could predict the effectiveness of the second-line cisplatin-based chemotherapy in pretreated patients with metastatic non-small cell lung cancer | journal = J Thorac Oncol | volume = 7 | issue = 4 | pages = 663–71 | date = april 2012 | pmid = 22425915 | doi = 10.1097/JTO.0b013e318244bdd4 | doi-access = free }}</ref> Ova korelacija implicira da nizak BRCA1 u karcinomu i posljedično nizak nivo popravljanja DNK uzrokuju ranjivost raka na liječenje pomoću DNK agenasa za umrežavanje. Visok BRCA1 može zaštititi ćelije raka, djelujući na put koji uklanja oštećenja u DNK koju unose lijekovi od platine. Stoga je nivo ekspresije '' BRCA1 '' potencijalno važan alat za prilagođavanje hemoterapije u upravljanju karcinomom pluća.

Nivo ekspresije '' BRCA1 '' je također važan za liječenje raka jajnika. Pacijenti sa sporadičnim karcinomom jajnika koji su liječeni lijekovima od platine imali su duže medijane vremena preživljavanja ako je njihova ekspresija '' BRCA1 '' bila niska u odnosu na pacijente sa jačom ekspresijom '' BRCA1 '' (46 u odnosu na 33 mjeseca).<ref name="pmid19035454">{{cite journal | vauthors = Weberpals J, Garbuio K, O'Brien A, Clark-Knowles K, Doucette S, Antoniouk O, Goss G, Dimitroulakos J | title = The DNA repair proteins BRCA1 and ERCC1 as predictive markers in sporadic ovarian cancer | journal = Int. J. Cancer | volume = 124 | issue = 4 | pages = 806–15 | date = februar 2009 | pmid = 19035454 | doi = 10.1002/ijc.23987 | s2cid = 13357407 | doi-access = free }}</ref>

== Interakcije ==
Pokazalo se da BRCA1 [[interakcija protein-protein|komunicira]] sa sljedećim proteinima:
{{refbegin|3}}
* [[ABL1]]<ref name="pmid12024016">{{cite journal | vauthors = Foray N, Marot D, Randrianarison V, Venezia ND, Picard D, Perricaudet M, Favaudon V, Jeggo P | title = Constitutive association of BRCA1 and c-Abl and its ATM-dependent disruption after irradiation | journal = Mol. Cell. Biol. | volume = 22 | issue = 12 | pages = 4020–32 | date = juni 2002 | pmid = 12024016 | pmc = 133860 | doi = 10.1128/MCB.22.12.4020-4032.2002 }}</ref>
* [[AKT1]]<ref name="pmid10542266">{{cite journal | vauthors = Altiok S, Batt D, Altiok N, Papautsky A, Downward J, Roberts TM, Avraham H | title = Heregulin induces phosphorylation of BRCA1 through phosphatidylinositol 3-Kinase/AKT in breast cancer cells | journal = J. Biol. Chem. | volume = 274 | issue = 45 | pages = 32274–8 | date = novembar 1999 | pmid = 10542266 | doi = 10.1074/jbc.274.45.32274 | doi-access = free }}</ref><ref name="pmid19074868">{{cite journal | vauthors = Xiang T, Ohashi A, Huang Y, Pandita TK, Ludwig T, Powell SN, Yang Q | title = Negative Regulation of AKT Activation by BRCA1 | journal = Cancer Res. | volume = 68 | issue = 24 | pages = 10040–4 | date = decembar 2008 | pmid = 19074868 | pmc = 2605656 | doi = 10.1158/0008-5472.CAN-08-3009 }}</ref>
* [[Androgenski receptor|AR]]<ref name="pmid11016951">{{cite journal | vauthors = Yeh S, Hu YC, Rahman M, Lin HK, Hsu CL, Ting HJ, Kang HY, Chang C | title = Increase of androgen-induced cell death and androgen receptor transactivation by BRCA1 in prostate cancer cells | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 97 | issue = 21 | pages = 11256–61 | date = oktobar 2000 | pmid = 11016951 | pmc = 17187 | doi = 10.1073/pnas.190353897 | bibcode = 2000PNAS...9711256Y }}</ref>
* [[ATR]]<ref name=pmid10608806/><ref name=pmid11114888/><ref name=pmid11016625/><ref name=pmid11278964/>
* [[ATM]]<ref name=pmid10783165/><ref name="pmid10608806">{{cite journal | vauthors = Kim ST, Lim DS, Canman CE, Kastan MB | title = Substrate specificities and identification of putative substrates of ATM kinase family members | journal = J. Biol. Chem. | volume = 274 | issue = 53 | pages = 37538–43 | date = decembar 1999 | pmid = 10608806 | doi = 10.1074/jbc.274.53.37538 | doi-access = free }}</ref><ref name="pmid11114888">{{cite journal | vauthors = Tibbetts RS, Cortez D, Brumbaugh KM, Scully R, Livingston D, Elledge SJ, Abraham RT | title = Functional interactions between BRCA1 and the checkpoint kinase ATR during genotoxic stress | journal = Genes Dev. | volume = 14 | issue = 23 | pages = 2989–3002 | date = decembar 2000 | pmid = 11114888 | pmc = 317107 | doi = 10.1101/gad.851000 }}</ref><ref name="pmid11016625">{{cite journal | vauthors = Chen J | title = Ataxia telangiectasia-related protein is involved in the phosphorylation of BRCA1 following deoxyribonucleic acid damage | journal = Cancer Res. | volume = 60 | issue = 18 | pages = 5037–9 | date = septembar 2000 | pmid = 11016625 }}</ref><ref name="pmid11278964">{{cite journal | vauthors = Gatei M, Zhou BB, Hobson K, Scott S, Young D, Khanna KK | title = Ataxia telangiectasia mutated (ATM) kinase and ATM and Rad3 related kinase mediate phosphorylation of Brca1 at distinct and overlapping sites. In vivo assessment using phospho-specific antibodies | journal = J. Biol. Chem. | volume = 276 | issue = 20 | pages = 17276–80 | date = maj 2001 | pmid = 11278964 | doi = 10.1074/jbc.M011681200 | doi-access = free }}</ref><ref name="pmid10866324">{{cite journal | vauthors = Gatei M, Scott SP, Filippovitch I, Soronika N, Lavin MF, Weber B, Khanna KK | title = Role for ATM in DNA damage-induced phosphorylation of BRCA1 | journal = Cancer Res. | volume = 60 | issue = 12 | pages = 3299–304 | date = juni 2000 | pmid = 10866324 }}</ref><ref name="pmid10550055">{{cite journal | vauthors = Cortez D, Wang Y, Qin J, Elledge SJ | title = Requirement of ATM-dependent phosphorylation of brca1 in the DNA damage response to double-strand breaks | journal = Science | volume = 286 | issue = 5442 | pages = 1162–6 | date = novembar 1999 | pmid = 10550055 | doi = 10.1126/science.286.5442.1162 }}</ref>
* [[ATF1]]<ref name="pmid10945975">{{cite journal | vauthors = Houvras Y, Benezra M, Zhang H, Manfredi JJ, Weber BL, Licht JD | title = BRCA1 physically and functionally interacts with ATF1 | journal = J. Biol. Chem. | volume = 275 | issue = 46 | pages = 36230–7 | date = novembar 2000 | pmid = 10945975 | doi = 10.1074/jbc.M002539200 | doi-access = free }}</ref>
* [[BACH1]]<ref name=pmid11301010/>
* [[BARD1]]<ref name="pmid11498787"/><ref name="pmid9788437" /><ref name="pmid11301010">{{cite journal | vauthors = Cantor SB, Bell DW, Ganesan S, Kass EM, Drapkin R, Grossman S, Wahrer DC, Sgroi DC, Lane WS, Haber DA, Livingston DM | title = BACH1, a novel helicase-like protein, interacts directly with BRCA1 and contributes to its DNA repair function | journal = Cell | volume = 105 | issue = 1 | pages = 149–60 | date = april 2001 | pmid = 11301010 | doi = 10.1016/S0092-8674(01)00304-X | doi-access = free }}</ref>
* [[BRCA2]]<ref name=pmid14636569/><ref name=pmid9774970/><ref name=pmid14499622/><ref name="pmid11477095">{{cite journal | vauthors = Sarkisian CJ, Master SR, Huber LJ, Ha SI, Chodosh LA | title = Analysis of murine Brca2 reveals conservation of protein–protein interactions but differences in nuclear localization signals | journal = J. Biol. Chem. | volume = 276 | issue = 40 | pages = 37640–8 | date = oktobar 2001 | pmid = 11477095 | doi = 10.1074/jbc.M106281200 | doi-access = free }}</ref>
* [[BRCC3]]<ref name=pmid14636569/>
* [[BRE (gene)|BRE]]<ref name=pmid14636569/>
* [[BRIP1]]<ref name=pmid14578343/><ref name=pmid15208681/><ref name="pmid15242590">{{cite journal | vauthors = Botuyan MV, Nominé Y, Yu X, Juranic N, Macura S, Chen J, Mer G | title = Structural basis of BACH1 phosphopeptide recognition by BRCA1 tandem BRCT domains | journal = Structure | volume = 12 | issue = 7 | pages = 1137–46 | date = juli 2004 | pmid = 15242590 | pmc = 3652423 | doi = 10.1016/j.str.2004.06.002 }}</ref><ref name="pmid14576433">{{cite journal | vauthors = Yu X, Chini CC, He M, Mer G, Chen J | title = The BRCT domain is a phospho-protein binding domain | journal = Science | volume = 302 | issue = 5645 | pages = 639–42 | date = oktobar 2003 | pmid = 14576433 | doi = 10.1126/science.1088753 | bibcode = 2003Sci...302..639Y | s2cid = 29407635 }}</ref><ref name="pmid15133502">{{cite journal | vauthors = Clapperton JA, Manke IA, Lowery DM, Ho T, Haire LF, Yaffe MB, Smerdon SJ | title = Structure and mechanism of BRCA1 BRCT domain recognition of phosphorylated BACH1 with implications for cancer | journal = Nature Structural & Molecular Biology | volume = 11 | issue = 6 | pages = 512–8 | date = juni 2004 | pmid = 15133502 | doi = 10.1038/nsmb775 | s2cid = 7354915 }}</ref>
* [[C-jun]]<ref name=pmid12080089/>
* [[CHEK2]]<ref name="pmid10724175">{{cite journal | vauthors = Lee JS, Collins KM, Brown AL, Lee CH, Chung JH | title = hCds1-mediated phosphorylation of BRCA1 regulates the DNA damage response | journal = Nature | volume = 404 | issue = 6774 | pages = 201–4 | date = mart 2000 | pmid = 10724175 | doi = 10.1038/35004614 | bibcode = 2000Natur.404..201L | s2cid = 4345911 }}</ref><ref name="pmid18804494">{{cite journal | vauthors = Chabalier-Taste C, Racca C, Dozier C, Larminat F | title = BRCA1 is regulated by Chk2 in response to spindle damage | journal = Biochim. Biophys. Acta | volume = 1783 | issue = 12 | pages = 2223–33 | date = decembar 2008 | pmid = 18804494 | doi = 10.1016/j.bbamcr.2008.08.006 | doi-access = free }}</ref>
* [[CLSPN]]<ref name="pmid15096610">{{cite journal | vauthors = Lin SY, Li K, Stewart GS, Elledge SJ | title = Human Claspin works with BRCA1 to both positively and negatively regulate cell proliferation | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 101 | issue = 17 | pages = 6484–9 | date = april 2004 | pmid = 15096610 | pmc = 404071 | doi = 10.1073/pnas.0401847101 | bibcode = 2004PNAS..101.6484L }}</ref>
* [[COBRA1]]<ref name="pmid11739404">{{cite journal | vauthors = Ye Q, Hu YF, Zhong H, Nye AC, Belmont AS, Li R | title = BRCA1-induced large-scale chromatin unfolding and allele-specific effects of cancer-predisposing mutations | journal = J. Cell Biol. | volume = 155 | issue = 6 | pages = 911–21 | date = decembar 2001 | pmid = 11739404 | pmc = 2150890 | doi = 10.1083/jcb.200108049 }}</ref>
* [[CREBBP]]<ref name="pmid12700228">{{cite journal | vauthors = Benezra M, Chevallier N, Morrison DJ, MacLachlan TK, El-Deiry WS, Licht JD | title = BRCA1 augments transcription by the NF-kappaB transcription factor by binding to the Rel domain of the p65/RelA subunit | journal = J. Biol. Chem. | volume = 278 | issue = 29 | pages = 26333–41 | date = juli 2003 | pmid = 12700228 | doi = 10.1074/jbc.M303076200 | doi-access = free }}</ref><ref name="pmid10655477">{{cite journal | vauthors = Pao GM, Janknecht R, Ruffner H, Hunter T, Verma IM | title = CBP/p300 interact with and function as transcriptional coactivators of BRCA1 | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 97 | issue = 3 | pages = 1020–5 | date = februar 2000 | pmid = 10655477 | pmc = 15508 | doi = 10.1073/pnas.97.3.1020 | bibcode = 2000PNAS...97.1020P }}</ref><ref name="pmid9926942">{{cite journal | vauthors = Chai YL, Cui J, Shao N, Shyam E, Reddy P, Rao VN | title = The second BRCT domain of BRCA1 proteins interacts with p53 and stimulates transcription from the p21WAF1/CIP1 promoter | journal = Oncogene | volume = 18 | issue = 1 | pages = 263–8 | date = januar 1999 | pmid = 9926942 | doi = 10.1038/sj.onc.1202323 | doi-access = free }}</ref><ref name="pmid11782371">{{cite journal | vauthors = Fan S, Ma YX, Wang C, Yuan RQ, Meng Q, Wang JA, Erdos M, Goldberg ID, Webb P, Kushner PJ, Pestell RG, Rosen EM | title = p300 Modulates the BRCA1 inhibition of estrogen receptor activity | journal = Cancer Res. | volume = 62 | issue = 1 | pages = 141–51 | date = januar 2002 | pmid = 11782371 }}</ref><ref name="pmid9443979">{{cite journal | vauthors = Neish AS, Anderson SF, Schlegel BP, Wei W, Parvin JD | title = Factors associated with the mammalian RNA polymerase II holoenzyme | journal = Nucleic Acids Res. | volume = 26 | issue = 3 | pages = 847–53 | date = februar 1998 | pmid = 9443979 | pmc = 147327 | doi = 10.1093/nar/26.3.847 }}</ref>
* [[CSNK2B]]<ref name="pmid10403822">{{cite journal | vauthors = O'Brien KA, Lemke SJ, Cocke KS, Rao RN, Beckmann RP | title = Casein kinase 2 binds to and phosphorylates BRCA1 | journal = Biochem. Biophys. Res. Commun. | volume = 260 | issue = 3 | pages = 658–64 | date = juli 1999 | pmid = 10403822 | doi = 10.1006/bbrc.1999.0892 }}</ref>
* [[CSTF2]]<ref name="pmid11257228">{{cite journal | vauthors = Kleiman FE, Manley JL | title = The BARD1-CstF-50 interaction links mRNA 3' end formation to DNA damage and tumor suppression | journal = Cell | volume = 104 | issue = 5 | pages = 743–53 | date = mart 2001 | pmid = 11257228 | doi = 10.1016/S0092-8674(01)00270-7 | doi-access = free }}</ref><ref name="pmid10477523">{{cite journal | vauthors = Kleiman FE, Manley JL | title = Functional interaction of BRCA1-associated BARD1 with polyadenylation factor CstF-50 | journal = Science | volume = 285 | issue = 5433 | pages = 1576–9 | date = septembar 1999 | pmid = 10477523 | doi = 10.1126/science.285.5433.1576 }}</ref>
* [[CDK2]]<ref name="pmid9244350">{{cite journal | vauthors = Wang H, Shao N, Ding QM, Cui J, Reddy ES, Rao VN | title = BRCA1 proteins are transported to the nucleus in the absence of serum and splice variants BRCA1a, BRCA1b are tyrosine phosphoproteins that associate with E2F, cyclins and cyclin dependent kinases | journal = Oncogene | volume = 15 | issue = 2 | pages = 143–57 | date = Jul 1997 | pmid = 9244350 | doi = 10.1038/sj.onc.1201252 | doi-access = free }}</ref><ref name="pmid8764100">{{cite journal | vauthors = Chen Y, Farmer AA, Chen CF, Jones DC, Chen PL, Lee WH | title = BRCA1 is a 220-kDa nuclear phosphoprotein that is expressed and phosphorylated in a cell cycle-dependent manner | journal = Cancer Res. | volume = 56 | issue = 14 | pages = 3168–72 | date = juli 1996 | pmid = 8764100 }}</ref><ref name="pmid10373534">{{cite journal | vauthors = Ruffner H, Jiang W, Craig AG, Hunter T, Verma IM | title = BRCA1 is phosphorylated at serine 1497 in vivo at a cyclin-dependent kinase 2 phosphorylation site | journal = Mol. Cell. Biol. | volume = 19 | issue = 7 | pages = 4843–54 | date = juli 1999 | pmid = 10373534 | pmc = 84283 | doi = 10.1128/MCB.19.7.4843}}</ref>
* [[DHX9]]<ref name="pmid12592385">{{cite journal | vauthors = Schlegel BP, Starita LM, Parvin JD | title = Overexpression of a protein fragment of RNA helicase A causes inhibition of endogenous BRCA1 function and defects in ploidy and cytokinesis in mammary epithelial cells | journal = Oncogene | volume = 22 | issue = 7 | pages = 983–91 | date = februar 2003 | pmid = 12592385 | doi = 10.1038/sj.onc.1206195 | doi-access = free }}</ref><ref name="pmid9662397">{{cite journal | vauthors = Anderson SF, Schlegel BP, Nakajima T, Wolpin ES, Parvin JD | title = BRCA1 protein is linked to the RNA polymerase II holoenzyme complex via RNA helicase A | journal = Nat. Genet. | volume = 19 | issue = 3 | pages = 254–6 | date = juli 1998 | pmid = 9662397 | doi = 10.1038/930 | s2cid = 10953768 }}</ref>
* [[ELK4]]<ref name="pmid11313879">{{cite journal | vauthors = Chai Y, Chipitsyna G, Cui J, Liao B, Liu S, Aysola K, Yezdani M, Reddy ES, Rao VN | title = c-Fos oncogene regulator Elk-1 interacts with BRCA1 splice variants BRCA1a/1b and enhances BRCA1a/1b-mediated growth suppression in breast cancer cells | journal = Oncogene | volume = 20 | issue = 11 | pages = 1357–67 | date = mart 2001 | pmid = 11313879 | doi = 10.1038/sj.onc.1204256 | doi-access = free }}</ref>
* [[EP300]]<ref name=pmid10655477/><ref name=pmid11782371/>
* [[Estrogen receptor alpha|ESR1]]<ref name=pmid11782371/><ref name="pmid11493692">{{cite journal | vauthors = Zheng L, Annab LA, Afshari CA, Lee WH, Boyer TG | title = BRCA1 mediates ligand-independent transcriptional repression of the estrogen receptor | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 98 | issue = 17 | pages = 9587–92 | date = august 2001 | pmid = 11493692 | pmc = 55496 | doi = 10.1073/pnas.171174298 | bibcode = 2001PNAS...98.9587Z }}</ref><ref name="pmid11244506">{{cite journal | vauthors = Fan S, Ma YX, Wang C, Yuan RQ, Meng Q, Wang JA, Erdos M, Goldberg ID, Webb P, Kushner PJ, Pestell RG, Rosen EM | title = Role of direct interaction in BRCA1 inhibition of estrogen receptor activity | journal = Oncogene | volume = 20 | issue = 1 | pages = 77–87 | date = januar 2001 | pmid = 11244506 | doi = 10.1038/sj.onc.1204073 | doi-access = free }}</ref><ref name="pmid12400015">{{cite journal | vauthors = Kawai H, Li H, Chun P, Avraham S, Avraham HK | title = Direct interaction between BRCA1 and the estrogen receptor regulates vascular endothelial growth factor (VEGF) transcription and secretion in breast cancer cells | journal = Oncogene | volume = 21 | issue = 50 | pages = 7730–9 | date = oktobar 2002 | pmid = 12400015 | doi = 10.1038/sj.onc.1205971 | doi-access = free }}</ref>
* [[FANCA]]<ref name="pmid12354784">{{cite journal | vauthors = Folias A, Matkovic M, Bruun D, Reid S, Hejna J, Grompe M, D'Andrea A, Moses R | title = BRCA1 interacts directly with the Fanconi anemia protein FANCA | journal = Hum. Mol. Genet. | volume = 11 | issue = 21 | pages = 2591–7 | date = oktobar 2002 | pmid = 12354784 | doi = 10.1093/hmg/11.21.2591 | doi-access = free }}</ref>
* [[FANCD2]]<ref name="pmid14499622">{{cite journal | vauthors = Reuter TY, Medhurst AL, Waisfisz Q, Zhi Y, Herterich S, Hoehn H, Gross HJ, Joenje H, Hoatlin ME, Mathew CG, Huber PA | title = Yeast two-hybrid screens imply involvement of Fanconi anemia proteins in transcription regulation, cell signaling, oxidative metabolism, and cellular transport | journal = Exp. Cell Res. | volume = 289 | issue = 2 | pages = 211–21 | date = oktobar 2003 | pmid = 14499622 | doi = 10.1016/S0014-4827(03)00261-1 }}</ref><ref name=pmid12887909/>
* [[FHL2]]<ref name="pmid14550570">{{cite journal | vauthors = Yan J, Zhu J, Zhong H, Lu Q, Huang C, Ye Q | title = BRCA1 interacts with FHL2 and enhances FHL2 transactivation function | journal = FEBS Lett. | volume = 553 | issue = 1–2 | pages = 183–9 | date = oktobar 2003 | pmid = 14550570 | doi = 10.1016/S0014-5793(03)00978-5 | s2cid = 31566004 | doi-access = free }}</ref><ref name="pmid14986435">{{cite journal | vauthors = Yan JH, Ye QN, Zhu JH, Zhong HJ, Zheng HY, Huang CF | title = [Isolation and characterization of a BRCA1-interacting protein] | language = zh | journal = Yi Chuan Xue Bao | volume = 30 | issue = 12 | pages = 1161–6 | date = decembar 2003 | pmid = 14986435 }}</ref>
* [[H2AFX]]<ref name=pmid12485996/><ref name=pmid11927591/><ref name="pmid10959836">{{cite journal | vauthors = Paull TT, Rogakou EP, Yamazaki V, Kirchgessner CU, Gellert M, Bonner WM | title = A critical role for histone H2AX in recruitment of repair factors to nuclear foci after DNA damage | journal = Curr. Biol. | volume = 10 | issue = 15 | pages = 886–95 | year = 2000 | pmid = 10959836 | doi = 10.1016/S0960-9822(00)00610-2 | doi-access = free }}</ref>
* [[JUNB]]<ref name=pmid12080089/>
* [[JunD]]<ref name="pmid12080089">{{cite journal | vauthors = Hu YF, Li R | title = JunB potentiates function of BRCA1 activation domain 1 (AD1) through a coiled-coil-mediated interaction | journal = Genes Dev. | volume = 16 | issue = 12 | pages = 1509–17 | date = juni 2002 | pmid = 12080089 | pmc = 186344 | doi = 10.1101/gad.995502 }}</ref>
* [[LMO4]]<ref name="pmid12925972">{{cite journal | vauthors = Sutherland KD, Visvader JE, Choong DY, Sum EY, Lindeman GJ, Campbell IG | title = Mutational analysis of the LMO4 gene, encoding a BRCA1-interacting protein, in breast carcinomas | journal = Int. J. Cancer | volume = 107 | issue = 1 | pages = 155–8 | date = oktobar 2003 | pmid = 12925972 | doi = 10.1002/ijc.11343 | s2cid = 20908722 | doi-access = free }}</ref><ref name="pmid11751867">{{cite journal | vauthors = Sum EY, Peng B, Yu X, Chen J, Byrne J, Lindeman GJ, Visvader JE | title = The LIM domain protein LMO4 interacts with the cofactor CtIP and the tumor suppressor BRCA1 and inhibits BRCA1 activity | journal = J. Biol. Chem. | volume = 277 | issue = 10 | pages = 7849–56 | date = mart 2002 | pmid = 11751867 | doi = 10.1074/jbc.M110603200 | doi-access = free }}</ref>
* [[MAP3K3]]<ref name="pmid15205325">{{cite journal | vauthors = Gilmore PM, McCabe N, Quinn JE, Kennedy RD, Gorski JJ, Andrews HN, McWilliams S, Carty M, Mullan PB, Duprex WP, Liu ET, Johnston PG, Harkin DP | title = BRCA1 interacts with and is required for paclitaxel-induced activation of mitogen-activated protein kinase kinase kinase 3 | journal = Cancer Res. | volume = 64 | issue = 12 | pages = 4148–54 | date = juni 2004 | pmid = 15205325 | doi = 10.1158/0008-5472.CAN-03-4080 | doi-access = free }}</ref>
* [[MED1]]<ref name="pmid15208681">{{cite journal | vauthors = Wada O, Oishi H, Takada I, Yanagisawa J, Yano T, Kato S | title = BRCA1 function mediates a TRAP/DRIP complex through direct interaction with TRAP220 | journal = Oncogene | volume = 23 | issue = 35 | pages = 6000–5 | date = august 2004 | pmid = 15208681 | doi = 10.1038/sj.onc.1207786 | doi-access = free }}</ref>
* [[MED17]]<ref name=pmid15208681/><ref name="pmid11504724">{{cite journal | vauthors = Chiba N, Parvin JD | title = Redistribution of BRCA1 among four different protein complexes following replication blockage | journal = J. Biol. Chem. | volume = 276 | issue = 42 | pages = 38549–54 | date = oktobar 2001 | pmid = 11504724 | doi = 10.1074/jbc.M105227200 | doi-access = free }}</ref><ref name="pmid12154023">{{cite journal | vauthors = Chiba N, Parvin JD | title = The BRCA1 and BARD1 association with the RNA polymerase II holoenzyme | journal = Cancer Res. | volume = 62 | issue = 15 | pages = 4222–8 | date = august 2002 | pmid = 12154023 }}</ref>
* [[MED21]]<ref name="pmid9159119">{{cite journal | vauthors = Scully R, Anderson SF, Chao DM, Wei W, Ye L, Young RA, Livingston DM, Parvin JD | title = BRCA1 is a component of the RNA polymerase II holoenzyme | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 94 | issue = 11 | pages = 5605–10 | date = maj 1997 | pmid = 9159119 | pmc = 20825 | doi = 10.1073/pnas.94.11.5605 | bibcode = 1997PNAS...94.5605S }}</ref>
* [[MED24]]<ref name=pmid15208681/>
* [[MRE11A]]<ref name=pmid10783165/><ref name=pmid11504724/><ref name=pmid10426999/><ref name="pmid11353843">{{cite journal | vauthors = Paull TT, Cortez D, Bowers B, Elledge SJ, Gellert M | title = Direct DNA binding by Brca1 | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 98 | issue = 11 | pages = 6086–91 | date = maj 2001 | pmid = 11353843 | pmc = 33426 | doi = 10.1073/pnas.111125998 }}</ref>
* [[MSH2]]<ref name="pmid10783165">{{cite journal | vauthors = Wang Y, Cortez D, Yazdi P, Neff N, Elledge SJ, Qin J | title = BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures | journal = Genes Dev. | volume = 14 | issue = 8 | pages = 927–39 | date = april 2000 | pmid = 10783165 | pmc = 316544 | doi = 10.1101/gad.14.8.927| doi-broken-date = 31. 5. 2021 }}</ref><ref name="pmid11498787"/>
* [[MSH3]]<ref name="pmid11498787" /><ref name="pmid14578343">{{cite journal | vauthors = Rodriguez M, Yu X, Chen J, Songyang Z | title = Phosphopeptide binding specificities of BRCA1 COOH-terminal (BRCT) domains | journal = J. Biol. Chem. | volume = 278 | issue = 52 | pages = 52914–8 | date = decembar 2003 | pmid = 14578343 | doi = 10.1074/jbc.C300407200 | doi-access = free }}</ref>
* [[MSH6]]<ref name=pmid10783165/><ref name="pmid11498787"/>
* [[Myc]]<ref name="pmid9788437"/><ref name=pmid11916966/><ref name="pmid14612409">{{cite journal | vauthors = Xiong J, Fan S, Meng Q, Schramm L, Wang C, Bouzahza B, Zhou J, Zafonte B, Goldberg ID, Haddad BR, Pestell RG, Rosen EM | title = BRCA1 inhibition of telomerase activity in cultured cells | journal = Mol. Cell. Biol. | volume = 23 | issue = 23 | pages = 8668–90 | date = decembar 2003 | pmid = 14612409 | pmc = 262673 | doi = 10.1128/MCB.23.23.8668-8690.2003 }}</ref><ref name="pmid12646176">{{cite journal | vauthors = Zhou C, Liu J | title = Inhibition of human telomerase reverse transcriptase gene expression by BRCA1 in human ovarian cancer cells | journal = Biochem. Biophys. Res. Commun. | volume = 303 | issue = 1 | pages = 130–6 | date = mart 2003 | pmid = 12646176 | doi = 10.1016/S0006-291X(03)00318-8 }}</ref>
* [[Nibrin|NBN]]<ref name=pmid10783165/><ref name=pmid11504724/><ref name=pmid10426999/>
* [[N-myc-interactor|NMI]]<ref name="pmid11916966">{{cite journal | vauthors = Li H, Lee TH, Avraham H | title = A novel tricomplex of BRCA1, Nmi, and c-Myc inhibits c-Myc-induced human telomerase reverse transcriptase gene (hTERT) promoter activity in breast cancer | journal = J. Biol. Chem. | volume = 277 | issue = 23 | pages = 20965–73 | date = juni 2002 | pmid = 11916966 | doi = 10.1074/jbc.M112231200 | doi-access = free }}</ref>
* [[NPM1]]<ref name=pmid15184379/>
* [[NCOA2]]<ref name=pmid14578343/><ref name="pmid11085509">{{cite journal | vauthors = Park JJ, Irvine RA, Buchanan G, Koh SS, Park JM, Tilley WD, Stallcup MR, Press MF, Coetzee GA | title = Breast cancer susceptibility gene 1 (BRCAI) is a coactivator of the androgen receptor | journal = Cancer Res. | volume = 60 | issue = 21 | pages = 5946–9 | date = novembar 2000 | pmid = 11085509 }}</ref>
* [[NUFIP1]]<ref name="pmid15107825">{{cite journal | vauthors = Cabart P, Chew HK, Murphy S | title = BRCA1 cooperates with NUFIP and P-TEFb to activate transcription by RNA polymerase II | journal = Oncogene | volume = 23 | issue = 31 | pages = 5316–29 | date = juli 2004 | pmid = 15107825 | doi = 10.1038/sj.onc.1207684 | doi-access = free }}</ref>
* [[P53]]<ref name=pmid14636569/><ref name=pmid9926942/><ref name="pmid14710355">{{cite journal | vauthors = Abramovitch S, Werner H | title = Functional and physical interactions between BRCA1 and p53 in transcriptional regulation of the IGF-IR gene | journal = Horm. Metab. Res. | volume = 35 | issue = 11–12 | pages = 758–62 | year = 2003 | pmid = 14710355 | doi = 10.1055/s-2004-814154 }}</ref><ref name="pmid9482880">{{cite journal | vauthors = Ouchi T, Monteiro AN, August A, Aaronson SA, Hanafusa H | title = BRCA1 regulates p53-dependent gene expression | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 95 | issue = 5 | pages = 2302–6 | date = mart 1998 | pmid = 9482880 | pmc = 19327 | doi = 10.1073/pnas.95.5.2302 | bibcode = 1998PNAS...95.2302O }}</ref><ref name="pmid9582019">{{cite journal | vauthors = Zhang H, Somasundaram K, Peng Y, Tian H, Zhang H, Bi D, Weber BL, El-Deiry WS | title = BRCA1 physically associates with p53 and stimulates its transcriptional activity | journal = Oncogene | volume = 16 | issue = 13 | pages = 1713–21 | date = april 1998 | pmid = 9582019 | doi = 10.1038/sj.onc.1201932 | doi-access = free }}</ref>
* [[PALB2]]<ref name="pmid19369211">{{cite journal | vauthors = Sy SM, Huen MS, Chen J | title = PALB2 is an integral component of the BRCA complex required for homologous recombination repair | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 106 | issue = 17 | pages = 7155–60 | date = april 2009 | pmid = 19369211 | pmc = 2678481 | doi = 10.1073/pnas.0811159106 | bibcode = 2009PNAS..106.7155S }}</ref>
* [[POLR2A]]<ref name=pmid11504724/><ref name=pmid9159119/><ref name="pmid14506230">{{cite journal | vauthors = Krum SA, Miranda GA, Lin C, Lane TF | title = BRCA1 associates with processive RNA polymerase II | journal = J. Biol. Chem. | volume = 278 | issue = 52 | pages = 52012–20 | date = decembar 2003 | pmid = 14506230 | doi = 10.1074/jbc.M308418200 | doi-access = free }}</ref><ref name="pmid12955082">{{cite journal | vauthors = Krum SA, Womack JE, Lane TF | title = Bovine BRCA1 shows classic responses to genotoxic stress but low in vitro transcriptional activation activity | journal = Oncogene | volume = 22 | issue = 38 | pages = 6032–44 | date = septembar 2003 | pmid = 12955082 | doi = 10.1038/sj.onc.1206515 | doi-access = free }}</ref>
* [[PPP1CA]]<ref name="pmid12438214">{{cite journal | vauthors = Liu Y, Virshup DM, White RL, Hsu LC | title = Regulation of BRCA1 phosphorylation by interaction with protein phosphatase 1alpha | journal = Cancer Res. | volume = 62 | issue = 22 | pages = 6357–61 | date = novembar 2002 | pmid = 12438214 }}</ref>
* [[Rad50]]<ref name=pmid10783165/><ref name=pmid11504724/><ref name="pmid10426999">{{cite journal | vauthors = Zhong Q, Chen CF, Li S, Chen Y, Wang CC, Xiao J, Chen PL, Sharp ZD, Lee WH | title = Association of BRCA1 with the hRad50-hMre11-p95 complex and the DNA damage response | journal = Science | volume = 285 | issue = 5428 | pages = 747–50 | date = juli 1999 | pmid = 10426999 | doi = 10.1126/science.285.5428.747 }}</ref>
* [[RAD51]]<ref name="pmid11498787"/><ref name=pmid14636569/><ref name="pmid9774970">{{cite journal | vauthors = Chen J, Silver DP, Walpita D, Cantor SB, Gazdar AF, Tomlinson G, Couch FJ, Weber BL, Ashley T, Livingston DM, Scully R | title = Stable interaction between the products of the BRCA1 and BRCA2 tumor suppressor genes in mitotic and meiotic cells | journal = Mol. Cell | volume = 2 | issue = 3 | pages = 317–28 | date = septembar 1998 | pmid = 9774970 | doi = 10.1016/S1097-2765(00)80276-2 | doi-access = free }}</ref><ref name="pmid9008167">{{cite journal | vauthors = Scully R, Chen J, Plug A, Xiao Y, Weaver D, Feunteun J, Ashley T, Livingston DM | title = Association of BRCA1 with Rad51 in mitotic and meiotic cells | journal = Cell | volume = 88 | issue = 2 | pages = 265–75 | date = januar 1997 | pmid = 9008167 | doi = 10.1016/S0092-8674(00)81847-4 | doi-access = free }}</ref>
* [[RBBP4]]<ref name=pmid10220405/>
* [[RBBP7]]<ref name="pmid10220405">{{cite journal | vauthors = Yarden RI, Brody LC | title = BRCA1 interacts with components of the histone deacetylase complex | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 96 | issue = 9 | pages = 4983–8 | date = april 1999 | pmid = 10220405 | pmc = 21803 | doi = 10.1073/pnas.96.9.4983 | bibcode = 1999PNAS...96.4983Y }}</ref><ref name="pmid11394910">{{cite journal | vauthors = Chen GC, Guan LS, Yu JH, Li GC, Choi Kim HR, Wang ZY | title = Rb-associated protein 46 (RbAp46) inhibits transcriptional transactivation mediated by BRCA1 | journal = Biochem. Biophys. Res. Commun. | volume = 284 | issue = 2 | pages = 507–14 | date = juni 2001 | pmid = 11394910 | doi = 10.1006/bbrc.2001.5003 }}</ref><ref name="pmid11746496">{{cite journal | vauthors = Yarden RI, Brody LC | title = Identification of proteins that interact with BRCA1 by Far-Western library screening | journal = J. Cell. Biochem. | volume = 83 | issue = 4 | pages = 521–31 | year = 2001 | pmid = 11746496 | doi = 10.1002/jcb.1257 | s2cid = 29703139 | url = https://zenodo.org/record/1229223 }}</ref>
* [[RBBP8]]<ref name=pmid14578343/><ref name="pmid9738006">{{cite journal | vauthors = Yu X, Wu LC, Bowcock AM, Aronheim A, Baer R | title = The C-terminal (BRCT) domains of BRCA1 interact in vivo with CtIP, a protein implicated in the CtBP pathway of transcriptional repression | journal = J. Biol. Chem. | volume = 273 | issue = 39 | pages = 25388–92 | date = septembar 1998 | pmid = 9738006 | doi = 10.1074/jbc.273.39.25388 | doi-access = free }}</ref><ref name="pmid10196224">{{cite journal | vauthors = Li S, Chen PL, Subramanian T, Chinnadurai G, Tomlinson G, Osborne CK, Sharp ZD, Lee WH | title = Binding of CtIP to the BRCT repeats of BRCA1 involved in the transcription regulation of p21 is disrupted upon DNA damage | journal = J. Biol. Chem. | volume = 274 | issue = 16 | pages = 11334–8 | date = april 1999 | pmid = 10196224 | doi = 10.1074/jbc.274.16.11334 | doi-access = free }}</ref><ref name="pmid9811458">{{cite journal | vauthors = Wong AK, Ormonde PA, Pero R, Chen Y, Lian L, Salada G, Berry S, Lawrence Q, Dayananth P, Ha P, Tavtigian SV, Teng DH, Bartel PL | title = Characterization of a carboxy-terminal BRCA1 interacting protein | journal = Oncogene | volume = 17 | issue = 18 | pages = 2279–85 | date = novembar 1998 | pmid = 9811458 | doi = 10.1038/sj.onc.1202150 | doi-access = free }}</ref><ref name="pmid10910365">{{cite journal | vauthors = Li S, Ting NS, Zheng L, Chen PL, Ziv Y, Shiloh Y, Lee EY, Lee WH | title = Functional link of BRCA1 and ataxia telangiectasia gene product in DNA damage response | journal = Nature | volume = 406 | issue = 6792 | pages = 210–5 | date = juli 2000 | pmid = 10910365 | doi = 10.1038/35018134 | bibcode = 2000Natur.406..210L | s2cid = 3266654 }}</ref><ref name="pmid11689934">{{cite journal | vauthors = Wu-Baer F, Baer R | title = Effect of DNA damage on a BRCA1 complex | journal = Nature | volume = 414 | issue = 6859 | page = 36 | date = novembar 2001 | pmid = 11689934 | doi = 10.1038/35102118 | s2cid = 4329675 }}</ref><ref name="pmid10764811">{{cite journal | vauthors = Yu X, Baer R | title = Nuclear localization and cell cycle-specific expression of CtIP, a protein that associates with the BRCA1 tumor suppressor | journal = J. Biol. Chem. | volume = 275 | issue = 24 | pages = 18541–9 | date = juni 2000 | pmid = 10764811 | doi = 10.1074/jbc.M909494199 | doi-access = free }}</ref>
* [[RELA]]<ref name=pmid12700228/>
* [[RB1]]<ref name=pmid10220405/><ref name=pmid11521194/><ref name="pmid10518542">{{cite journal | vauthors = Aprelikova ON, Fang BS, Meissner EG, Cotter S, Campbell M, Kuthiala A, Bessho M, Jensen RA, Liu ET | title = BRCA1-associated growth arrest is RB-dependent | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 96 | issue = 21 | pages = 11866–71 | date = oktobar 1999 | pmid = 10518542 | pmc = 18378 | doi = 10.1073/pnas.96.21.11866 | bibcode = 1999PNAS...9611866A }}</ref>
* [[RBL1]]<ref name=pmid11521194/>
* [[RBL2]]<ref name="pmid11521194">{{cite journal | vauthors = Fan S, Yuan R, Ma YX, Xiong J, Meng Q, Erdos M, Zhao JN, Goldberg ID, Pestell RG, Rosen EM | title = Disruption of BRCA1 LXCXE motif alters BRCA1 functional activity and regulation of RB family but not RB protein binding | journal = Oncogene | volume = 20 | issue = 35 | pages = 4827–41 | date = august 2001 | pmid = 11521194 | doi = 10.1038/sj.onc.1204666 | doi-access = free }}</ref>
* [[RPL31]]<ref name=pmid11746496/>
* [[SMARCA4]]<ref name=pmid10943845/><ref name="pmid15034933">{{cite journal | vauthors = Hill DA, de la Serna IL, Veal TM, Imbalzano AN | title = BRCA1 interacts with dominant negative SWI/SNF enzymes without affecting homologous recombination or radiation-induced gene activation of p21 or Mdm2 | journal = J. Cell. Biochem. | volume = 91 | issue = 5 | pages = 987–98 | date = april 2004 | pmid = 15034933 | doi = 10.1002/jcb.20003 | s2cid = 40668596 }}</ref>
* [[SMARCB1]]<ref name="pmid10943845">{{cite journal | vauthors = Bochar DA, Wang L, Beniya H, Kinev A, Xue Y, Lane WS, Wang W, Kashanchi F, Shiekhattar R | title = BRCA1 is associated with a human SWI/SNF-related complex: linking chromatin remodeling to breast cancer | journal = Cell | volume = 102 | issue = 2 | pages = 257–65 | date = juli 2000 | pmid = 10943845 | doi = 10.1016/S0092-8674(00)00030-1 | doi-access = free }}</ref>
* [[STAT1]]<ref name="pmid10792030">{{cite journal | vauthors = Ouchi T, Lee SW, Ouchi M, Aaronson SA, Horvath CM | title = Collaboration of signal transducer and activator of transcription 1 (STAT1) and BRCA1 in differential regulation of IFN-gamma target genes | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 97 | issue = 10 | pages = 5208–13 | date = maj 2000 | pmid = 10792030 | pmc = 25807 | doi = 10.1073/pnas.080469697 | bibcode = 2000PNAS...97.5208O }}</ref>
* [[UBE2D1]]<ref name="pmid14636569">{{cite journal | vauthors = Dong Y, Hakimi MA, Chen X, Kumaraswamy E, Cooch NS, Godwin AK, Shiekhattar R | title = Regulation of BRCC, a holoenzyme complex containing BRCA1 and BRCA2, by a signalosome-like subunit and its role in DNA repair | journal = Mol. Cell | volume = 12 | issue = 5 | pages = 1087–99 | date = novembar 2003 | pmid = 14636569 | doi = 10.1016/S1097-2765(03)00424-6 | doi-access = free }}</ref><ref name="pmid12887909">{{cite journal | vauthors = Vandenberg CJ, Gergely F, Ong CY, Pace P, Mallery DL, Hiom K, Patel KJ | title = BRCA1-independent ubiquitination of FANCD2 | journal = Mol. Cell | volume = 12 | issue = 1 | pages = 247–54 | date = juli 2003 | pmid = 12887909 | doi = 10.1016/S1097-2765(03)00281-8 | doi-access = free }}</ref><ref name="pmid12485996">{{cite journal | vauthors = Mallery DL, Vandenberg CJ, Hiom K | title = Activation of the E3 ligase function of the BRCA1/BARD1 complex by polyubiquitin chains | journal = EMBO J. | volume = 21 | issue = 24 | pages = 6755–62 | date = decembar 2002 | pmid = 12485996 | pmc = 139111 | doi = 10.1093/emboj/cdf691 }}</ref><ref name="pmid11927591">{{cite journal | vauthors = Chen A, Kleiman FE, Manley JL, Ouchi T, Pan ZQ | title = Autoubiquitination of the BRCA1*BARD1 RING ubiquitin ligase | journal = J. Biol. Chem. | volume = 277 | issue = 24 | pages = 22085–92 | date = juni 2002 | pmid = 11927591 | doi = 10.1074/jbc.M201252200 | doi-access = free }}</ref><ref name="pmid15184379">{{cite journal | vauthors = Sato K, Hayami R, Wu W, Nishikawa T, Nishikawa H, Okuda Y, Ogata H, Fukuda M, Ohta T | title = Nucleophosmin/B23 is a candidate substrate for the BRCA1-BARD1 ubiquitin ligase | journal = J. Biol. Chem. | volume = 279 | issue = 30 | pages = 30919–22 | date = juli 2004 | pmid = 15184379 | doi = 10.1074/jbc.C400169200 | doi-access = free }}</ref><ref name="pmid12732733">{{cite journal | vauthors = Brzovic PS, Keeffe JR, Nishikawa H, Miyamoto K, Fox D, Fukuda M, Ohta T, Klevit R | title = Binding and recognition in the assembly of an active BRCA1/BARD1 ubiquitin-ligase complex | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 100 | issue = 10 | pages = 5646–51 | date = maj 2003 | pmid = 12732733 | pmc = 156255 | doi = 10.1073/pnas.0836054100 | bibcode = 2003PNAS..100.5646B }}</ref><ref name="pmid14638690">{{cite journal | vauthors = Nishikawa H, Ooka S, Sato K, Arima K, Okamoto J, Klevit RE, Fukuda M, Ohta T | title = Mass spectrometric and mutational analyses reveal Lys-6-linked polyubiquitin chains catalyzed by BRCA1-BARD1 ubiquitin ligase | journal = J. Biol. Chem. | volume = 279 | issue = 6 | pages = 3916–24 | date = februar 2004 | pmid = 14638690 | doi = 10.1074/jbc.M308540200 | doi-access = free }}</ref><ref name="pmid12438698">{{cite journal | vauthors = Kentsis A, Gordon RE, Borden KL | title = Control of biochemical reactions through supramolecular RING domain self-assembly | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 99 | issue = 24 | pages = 15404–9 | date = novembar 2002 | pmid = 12438698 | pmc = 137729 | doi = 10.1073/pnas.202608799 | bibcode = 2002PNAS...9915404K }}</ref><ref name="pmid12890688">{{cite journal | vauthors = Wu-Baer F, Lagrazon K, Yuan W, Baer R | title = The BRCA1/BARD1 heterodimer assembles polyubiquitin chains through an unconventional linkage involving lysine residue K6 of ubiquitin | journal = J. Biol. Chem. | volume = 278 | issue = 37 | pages = 34743–6 | date = septembar 2003 | pmid = 12890688 | doi = 10.1074/jbc.C300249200 | doi-access = free }}</ref><ref name="pmid11278247">{{cite journal | vauthors = Hashizume R, Fukuda M, Maeda I, Nishikawa H, Oyake D, Yabuki Y, Ogata H, Ohta T | title = The RING heterodimer BRCA1-BARD1 is a ubiquitin ligase inactivated by a breast cancer-derived mutation | journal = J. Biol. Chem. | volume = 276 | issue = 18 | pages = 14537–40 | date = maj 2001 | pmid = 11278247 | doi = 10.1074/jbc.C000881200 | doi-access = free }}</ref>
* [[USF2]]<ref name="pmid14502648">{{cite journal | vauthors = Cable PL, Wilson CA, Calzone FJ, Rauscher FJ, Scully R, Livingston DM, Li L, Blackwell CB, Futreal PA, Afshari CA | title = Novel consensus DNA-binding sequence for BRCA1 protein complexes | journal = Mol. Carcinog. | volume = 38 | issue = 2 | pages = 85–96 | date = oktobar 2003 | pmid = 14502648 | doi = 10.1002/mc.10148 | s2cid = 24956554 | url = https://zenodo.org/record/1229285 }}</ref>
* [[VCP]]<ref name="pmid10855792">{{cite journal | vauthors = Zhang H, Wang Q, Kajino K, Greene MI | title = VCP, a weak ATPase involved in multiple cellular events, interacts physically with BRCA1 in the nucleus of living cells | journal = DNA Cell Biol. | volume = 19 | issue = 5 | pages = 253–63 | date = maj 2000 | pmid = 10855792 | doi = 10.1089/10445490050021168 }}</ref>
* [[XIST]]<ref name="pmid15065664">{{cite journal | vauthors = Ganesan S, Silver DP, Drapkin R, Greenberg R, Feunteun J, Livingston DM | title = Association of BRCA1 with the inactive X chromosome and XIST RNA | journal = Philos. Trans. R. Soc. Lond. B Biol. Sci. | volume = 359 | issue = 1441 | pages = 123–8 | date = januar 2004 | pmid = 15065664 | pmc = 1693294 | doi = 10.1098/rstb.2003.1371 }}</ref><ref name="pmid12419249">{{cite journal | vauthors = Ganesan S, Silver DP, Greenberg RA, Avni D, Drapkin R, Miron A, Mok SC, Randrianarison V, Brodie S, Salstrom J, Rasmussen TP, Klimke A, Marrese C, Marahrens Y, Deng CX, Feunteun J, Livingston DM | title = BRCA1 supports XIST RNA concentration on the inactive X chromosome | journal = Cell | volume = 111 | issue = 3 | pages = 393–405 | date = novembar 2002 | pmid = 12419249 | doi = 10.1016/S0092-8674(02)01052-8 | doi-access = free }}</ref> i
* [[ZNF350]]<ref name="pmid11090615">{{cite journal | vauthors = Zheng L, Pan H, Li S, Flesken-Nikitin A, Chen PL, Boyer TG, Lee WH | title = Sequence-specific transcriptional corepressor function for BRCA1 through a novel zinc finger protein, ZBRK1 | journal = Mol. Cell | volume = 6 | issue = 4 | pages = 757–68 | date = oktobar 2000 | pmid = 11090615 | doi = 10.1016/S1097-2765(00)00075-7 | doi-access = free }}</ref>
{{refend}}

==Reference==
{{reflist|30em}}

==Vanjski linkovi==
{{Commonscat|BRCA1}}
* {{MeshName|BRCA1+Protein|3=BRCA1 Protein}}
* {{MeshName|Genes,+BRCA1|3=Genes, BRCA1}}
* [https://www.ebi.ac.uk/pdbe/pdbe-kb/proteins/P38398 PDBe-KB] pruža pregled svih informacija o strukturi dostupnih u PDB za ljudsku BRCA1.

{{PDB Gallery|geneid=672}}
{{Geni supresije tumora}}
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[[Kategorija:Rak dojke]]
[[Kategorija:Geni na hromosomu 17]]
[[Kategorija:Ljudski proteini]]
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[[Kategorija:Geni supresije tumora]]
[[Kategorija:Proteomika]]