RECQL4
ATP-ovisna DNK-helikaza Q4 je enzim koji je kod ljudi kodiran genom RECQL4.[5][6][7]
Aminokiselinska sekvenca
urediDužina polipeptidnog lanca je 1.208 aminokiselina, а molekulska težina 133.077 Da.[8].
| 10 | 20 | 30 | 40 | 50 | ||||
|---|---|---|---|---|---|---|---|---|
| MERLRDVRER | LQAWERAFRR | QRGRRPSQDD | VEAAPEETRA | LYREYRTLKR | ||||
| TTGQAGGGLR | SSESLPAAAE | EAPEPRCWGP | HLNRAATKSP | QPTPGRSRQG | ||||
| SVPDYGQRLK | ANLKGTLQAG | PALGRRPWPL | GRASSKASTP | KPPGTGPVPS | ||||
| FAEKVSDEPP | QLPEPQPRPG | RLQHLQASLS | QRLGSLDPGW | LQRCHSEVPD | ||||
| FLGAPKACRP | DLGSEESQLL | IPGESAVLGP | GAGSQGPEAS | AFQEVSIRVG | ||||
| SPQPSSSGGE | KRRWNEEPWE | SPAQVQQESS | QAGPPSEGAG | AVAVEEDPPG | ||||
| EPVQAQPPQP | CSSPSNPRYH | GLSPSSQARA | GKAEGTAPLH | IFPRLARHDR | ||||
| GNYVRLNMKQ | KHYVRGRALR | SRLLRKQAWK | QKWRKKGECF | GGGGATVTTK | ||||
| ESCFLNEQFD | HWAAQCPRPA | SEEDTDAVGP | EPLVPSPQPV | PEVPSLDPTV | ||||
| LPLYSLGPSG | QLAETPAEVF | QALEQLGHQA | FRPGQERAVM | RILSGISTLL | ||||
| VLPTGAGKSL | CYQLPALLYS | RRSPCLTLVV | SPLLSLMDDQ | VSGLPPCLKA | ||||
| ACIHSGMTRK | QRESVLQKIR | AAQVHVLMLT | PEALVGAGGL | PPAAQLPPVA | ||||
| FACIDEAHCL | SQWSHNFRPC | YLRVCKVLRE | RMGVHCFLGL | TATATRRTAS | ||||
| DVAQHLAVAE | EPDLHGPAPV | PTNLHLSVSM | DRDTDQALLT | LLQGKRFQNL | ||||
| DSIIIYCNRR | EDTERIAALL | RTCLHAAWVP | GSGGRAPKTT | AEAYHAGMCS | ||||
| RERRRVQRAF | MQGQLRVVVA | TVAFGMGLDR | PDVRAVLHLG | LPPSFESYVQ | ||||
| AVGRAGRDGQ | PAHCHLFLQP | QGEDLRELRR | HVHADSTDFL | AVKRLVQRVF | ||||
| PACTCTCTRP | PSEQEGAVGG | ERPVPKYPPQ | EAEQLSHQAA | PGPRRVCMGH | ||||
| ERALPIQLTV | QALDMPEEAI | ETLLCYLELH | PHHWLELLAT | TYTHCRLNCP | ||||
| GGPAQLQALA | HRCPPLAVCL | AQQLPEDPGQ | GSSSVEFDMV | KLVDSMGWEL | ||||
| ASVRRALCQL | QWDHEPRTGV | RRGTGVLVEF | SELAFHLRSP | GDLTAEEKDQ | ||||
| ICDFLYGRVQ | ARERQALARL | RRTFQAFHSV | AFPSCGPCLE | QQDEERSTRL | ||||
| KDLLGRYFEE | EEGQEPGGME | DAQGPEPGQA | RLQDWEDQVR | CDIRQFLSLR | ||||
| PEEKFSSRAV | ARIFHGIGSP | CYPAQVYGQD | RRFWRKYLHL | SFHALVGLAT | ||||
| EELLQVAR |
Funkcija
urediMutacije 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]
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- ^ a b c GRCh38: Ensembl release 89: ENSG00000160957 - Ensembl, maj 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000033762 - Ensembl, maj 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ 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.
- ^ 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.
- ^ "Entrez Gene: RECQL4 RecQ protein-like 4".
- ^ "UniProt, O94761" (jezik: engleski). Pristupljeno 21. 9. 2021.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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- Kellermayer R (2006). "The versatile RECQL4". Genet. Med. 8 (4): 213–6. doi:10.1097/01.gim.0000214457.58378.1a. PMID 16617241.
- Soukup T (1976). "Intrafusal fibre types in rat limb muscle spindles: morphological and histochemical characteristics". Histochemistry. 47 (1): 43–57. doi:10.1007/BF00492992. PMID 133085. S2CID 23487130.
- Kitao S, Shimamoto A, Goto M, et al. (1999). "Mutations in RECQL4 cause a subset of cases of Rothmund-Thomson syndrome". Nat. Genet. 22 (1): 82–4. doi:10.1038/8788. PMID 10319867. S2CID 195211275.
- Yankiwski V, Marciniak RA, Guarente L, Neff NF (2000). "Nuclear structure in normal and Bloom syndrome cells". Proc. Natl. Acad. Sci. U.S.A. 97 (10): 5214–9. doi:10.1073/pnas.090525897. PMC 25808. PMID 10779560.
- Kawabe T, Tsuyama N, Kitao S, et al. (2000). "Differential regulation of human RecQ family helicases in cell transformation and cell cycle". Oncogene. 19 (41): 4764–72. doi:10.1038/sj.onc.1203841. PMID 11032027.
- Wang LL, Worley K, Gannavarapu A, et al. (2002). "Intron-size constraint as a mutational mechanism in Rothmund-Thomson syndrome". Am. J. Hum. Genet. 71 (1): 165–7. doi:10.1086/341234. PMC 384974. PMID 12016592.
- Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
- Roversi G, Beghini A, Zambruno G, et al. (2003). "Identification of two novel RECQL4exonic SNPs and genomic characterization of the IVS12 minisatellite". J. Hum. Genet. 48 (2): 107–9. doi:10.1007/s100380300016. PMID 12601557. S2CID 9960752.
- Wang LL, Gannavarapu A, Clericuzio CL, et al. (2004). "Absence of RECQL4 mutations in poikiloderma with neutropenia in Navajo and non-Navajo patients". Am. J. Med. Genet. A. 118 (3): 299–301. doi:10.1002/ajmg.a.10057. PMID 12673665. S2CID 36023058.
- Beghini A, Castorina P, Roversi G, et al. (2004). "RNA processing defects of the helicase gene RECQL4 in a compound heterozygous Rothmund-Thomson patient". Am. J. Med. Genet. A. 120 (3): 395–9. doi:10.1002/ajmg.a.20154. PMID 12838562. S2CID 25885145.
- Siitonen HA, Kopra O, Kääriäinen H, et al. (2004). "Molecular defect of RAPADILINO syndrome expands the phenotype spectrum of RECQL diseases". Hum. Mol. Genet. 12 (21): 2837–44. doi:10.1093/hmg/ddg306. PMID 12952869.
- Brandenberger R, Wei H, Zhang S, et al. (2005). "Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation". Nat. Biotechnol. 22 (6): 707–16. doi:10.1038/nbt971. PMID 15146197. S2CID 27764390.
- Nishijo K, Nakayama T, Aoyama T, et al. (2004). "Mutation analysis of the RECQL4 gene in sporadic osteosarcomas". Int. J. Cancer. 111 (3): 367–72. doi:10.1002/ijc.20269. PMID 15221963. S2CID 20389854.
- Yin J, Kwon YT, Varshavsky A, Wang W (2005). "RECQL4, mutated in the Rothmund-Thomson and RAPADILINO syndromes, interacts with ubiquitin ligases UBR1 and UBR2 of the N-end rule pathway". Hum. Mol. Genet. 13 (20): 2421–30. doi:10.1093/hmg/ddh269. PMID 15317757.
- Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
- Sengupta S, Shimamoto A, Koshiji M, et al. (2005). "Tumor suppressor p53 represses transcription of RECQ4 helicase". Oncogene. 24 (10): 1738–48. doi:10.1038/sj.onc.1208380. PMID 15674334.