RECQL4

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RECQL4
Dostupne strukture
PDBPretraga ortologa: PDBe RCSB
Spisak PDB ID kodova

2KMU

Identifikatori
AliasiRECQL4
Vanjski ID-jeviOMIM: 603780 MGI: 1931028 HomoloGene: 3144 GeneCards: RECQL4
Lokacija gena (čovjek)
Hromosom 8 (čovjek)
Hrom.Hromosom 8 (čovjek)[1]
Hromosom 8 (čovjek)
Genomska lokacija za RECQL4
Genomska lokacija za RECQL4
Bend8q24.3Početak144,511,288 bp[1]
Kraj144,517,845 bp[1]
Lokacija gena (miš)
Hromosom 15 (miš)
Hrom.Hromosom 15 (miš)[2]
Hromosom 15 (miš)
Genomska lokacija za RECQL4
Genomska lokacija za RECQL4
Bend15|15 D3Početak76,587,753 bp[2]
Kraj76,594,748 bp[2]
Obrazac RNK ekspresije
Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija ATP-dependent DNA/DNA annealing activity
nucleotide binding
GO:0043140 3'-5' DNA helicase activity
bubble DNA binding
GO:0001948, GO:0016582 protein binding
hydrolase activity
ATP binding
GO:0008026 helicase activity
nucleic acid binding
GO:1990163 four-way junction helicase activity
oxidized purine DNA binding
telomeric D-loop binding
DNA binding
single-stranded DNA binding
Ćelijska komponenta membrana
citoplazma
Jedro
Telomera
hromosom
Biološki proces multicellular organism development
GO:0100026 Popravka DNK
base-excision repair
double-strand break repair via homologous recombination
DNA recombination
Replikacija DNK
DNA duplex unwinding
telomeric D-loop disassembly
telomere maintenance
positive regulation of cell population proliferation
positive regulation of G2/M transition of mitotic cell cycle
positive regulation of DNA replication
DNA unwinding involved in DNA replication
Izvori:Amigo / QuickGO
Ortolozi
VrsteČovjekMiš
Entrez
Ensembl
UniProt
RefSeq (mRNK)

NM_004260

NM_058214

RefSeq (bjelančevina)

NP_004251

NP_478121

Lokacija (UCSC)Chr 8: 144.51 – 144.52 MbChr 15: 76.59 – 76.59 Mb
PubMed pretraga[3][4]
Wikipodaci
Pogledaj/uredi – čovjekPogledaj/uredi – miš

ATP-ovisna DNK-helikaza Q4 je enzim koji je kod ljudi kodiran genom RECQL4.[5][6][7]

Aminokiselinska sekvenca[uredi | uredi izvor]

Dužina polipeptidnog lanca je 1.208 aminokiselina, а molekulska težina 133.077 Da.[8].

1020304050
MERLRDVRERLQAWERAFRRQRGRRPSQDDVEAAPEETRALYREYRTLKR
TTGQAGGGLRSSESLPAAAEEAPEPRCWGPHLNRAATKSPQPTPGRSRQG
SVPDYGQRLKANLKGTLQAGPALGRRPWPLGRASSKASTPKPPGTGPVPS
FAEKVSDEPPQLPEPQPRPGRLQHLQASLSQRLGSLDPGWLQRCHSEVPD
FLGAPKACRPDLGSEESQLLIPGESAVLGPGAGSQGPEASAFQEVSIRVG
SPQPSSSGGEKRRWNEEPWESPAQVQQESSQAGPPSEGAGAVAVEEDPPG
EPVQAQPPQPCSSPSNPRYHGLSPSSQARAGKAEGTAPLHIFPRLARHDR
GNYVRLNMKQKHYVRGRALRSRLLRKQAWKQKWRKKGECFGGGGATVTTK
ESCFLNEQFDHWAAQCPRPASEEDTDAVGPEPLVPSPQPVPEVPSLDPTV
LPLYSLGPSGQLAETPAEVFQALEQLGHQAFRPGQERAVMRILSGISTLL
VLPTGAGKSLCYQLPALLYSRRSPCLTLVVSPLLSLMDDQVSGLPPCLKA
ACIHSGMTRKQRESVLQKIRAAQVHVLMLTPEALVGAGGLPPAAQLPPVA
FACIDEAHCLSQWSHNFRPCYLRVCKVLRERMGVHCFLGLTATATRRTAS
DVAQHLAVAEEPDLHGPAPVPTNLHLSVSMDRDTDQALLTLLQGKRFQNL
DSIIIYCNRREDTERIAALLRTCLHAAWVPGSGGRAPKTTAEAYHAGMCS
RERRRVQRAFMQGQLRVVVATVAFGMGLDRPDVRAVLHLGLPPSFESYVQ
AVGRAGRDGQPAHCHLFLQPQGEDLRELRRHVHADSTDFLAVKRLVQRVF
PACTCTCTRPPSEQEGAVGGERPVPKYPPQEAEQLSHQAAPGPRRVCMGH
ERALPIQLTVQALDMPEEAIETLLCYLELHPHHWLELLATTYTHCRLNCP
GGPAQLQALAHRCPPLAVCLAQQLPEDPGQGSSSVEFDMVKLVDSMGWEL
ASVRRALCQLQWDHEPRTGVRRGTGVLVEFSELAFHLRSPGDLTAEEKDQ
ICDFLYGRVQARERQALARLRRTFQAFHSVAFPSCGPCLEQQDEERSTRL
KDLLGRYFEEEEGQEPGGMEDAQGPEPGQARLQDWEDQVRCDIRQFLSLR
PEEKFSSRAVARIFHGIGSPCYPAQVYGQDRRFWRKYLHLSFHALVGLAT
EELLQVAR

Funkcija[uredi | uredi izvor]

Mutacije u RECQL4 povezane su s autosomno recesivnom bolešću Rothmund-Thomsonov sindrom, poremećajem koji ima obilježja preranog starenja.[9][10] Osim Rothmund-Thomsonovog sindroma, mutacije RECQL4 su također povezane sa RAPADILINO-om i Baller-Geroldovim sindromom.[11] Postoje dva tipa Rothmund-Thomsonovog sindroma, a tip 2 se javlja kod pacijenata koji nose štetne mutacije u obje kopije gena RECQL4. Ovo stanje je povezano s visokim rizikom od razvoja osteosarkoma (zloćudni tumor kostiju).[12] RECQL4 je imenovan po tome što je homologan (po podudarnosti sekvence) s ostalim članovima porodice RecQ-helikaza. Dvije druge genetičke bolesti su posljedica mutacija u drugim helikazama RECQ. Bloomov sindrom povezan je s mutacijama u BLM genu, a Wernerov sindrom s mutacijama u 'WRN genu.[13]

Popravak DNK[uredi | uredi izvor]

Dvolančani prekidi u DNK potencijalno su smrtonosni za ćeliju i moraju se popraviti. Popravljanje dvolančanih prekida pomoću homologne rekombinacije (HR) važan je ćelijski mehanizam za izbjegavanje ove smrtonosnosti. RECQL4 ima ključnu ulogu u prvom koraku HR -a, koji se naziva završna resekcija.[14] Kada je RECQL4 nedostatan, krajnja resekcija, a time i HR, se smanjuju. Dokazi ukazuju da drugi oblici popravljanja DNK, uključujući nehomologno spajanje krajeva, popravljanje ekscizije nukleotida i popravljanje ekscizije baza također ovise o funkciji RECQL4.[10] U Rothmund-Thomsonovom sindromu, povezanost deficitarne popravke DNK posredovane RECQL4 i preranog starenja u skladu je sa teorijom starenja oštećenjem DNK.

Reference[uredi | uredi izvor]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000160957 - Ensembl, maj 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000033762 - Ensembl, maj 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Kitao S, Ohsugi I, Ichikawa K, Goto M, Furuichi Y, Shimamoto A (Feb 1999). "Cloning of two new human helicase genes of the RecQ family: biological significance of multiple species in higher eukaryotes". Genomics. 54 (3): 443–52. doi:10.1006/geno.1998.5595. PMID 9878247.
  6. ^ Sangrithi MN, Bernal JA, Madine M, Philpott A, Lee J, Dunphy WG, Venkitaraman AR (Jun 2005). "Initiation of DNA replication requires the RECQL4 protein mutated in Rothmund-Thomson syndrome". Cell. 121 (6): 887–98. doi:10.1016/j.cell.2005.05.015. PMID 15960976. S2CID 15064074.
  7. ^ "Entrez Gene: RECQL4 RecQ protein-like 4".
  8. ^ "UniProt, O94761" (jezik: engleski). Pristupljeno 21. 9. 2021.
  9. ^ Lu H, Fang EF, Sykora P, Kulikowicz T, Zhang Y, Becker KG, Croteau DL, Bohr VA (2014). "Senescence induced by RECQL4 dysfunction contributes to Rothmund-Thomson syndrome features in mice". Cell Death Dis. 5 (5): e1226. doi:10.1038/cddis.2014.168. PMC 4047874. PMID 24832598.
  10. ^ a b Lu L, Jin W, Wang LL (2017). "Aging in Rothmund-Thomson syndrome and related RECQL4 genetic disorders". Ageing Res. Rev. 33: 30–35. doi:10.1016/j.arr.2016.06.002. PMID 27287744. S2CID 28321025.
  11. ^ Shamanna RA, Singh DK, Lu H, Mirey G, Keijzers G, Salles B, Croteau DL, Bohr VA (2014). "RECQ helicase RECQL4 participates in non-homologous end joining and interacts with the Ku complex". Carcinogenesis. 35 (11): 2415–24. doi:10.1093/carcin/bgu137. PMC 4216052. PMID 24942867.
  12. ^ Wang LL, Gannavarapu A, Kozinetz CA, et al. (2003). "Association between osteosarcoma and deleterious mutations in the RECQL4 gene in Rothmund-Thomson syndrome". J. Natl. Cancer Inst. 95 (9): 669–74. doi:10.1093/jnci/95.9.669. PMID 12734318.
  13. ^ Kitao S, Lindor NM, Shiratori M, et al. (2000). "Rothmund-thomson syndrome responsible gene, RECQL4: genomic structure and products". Genomics. 61 (3): 268–76. doi:10.1006/geno.1999.5959. PMID 10552928.
  14. ^ Lu H, Shamanna RA, Keijzers G, Anand R, Rasmussen LJ, Cejka P, Croteau DL, Bohr VA (2016). "RECQL4 Promotes DNA End Resection in Repair of DNA Double-Strand Breaks". Cell Rep. 16 (1): 161–73. doi:10.1016/j.celrep.2016.05.079. PMC 5576896. PMID 27320928.

Dopunska literatura[uredi | uredi izvor]

Vanjski linkovi[uredi | uredi izvor]