ATP-ovisna DNK-helikaza Q4 je enzim koji je kod ljudi kodiran genom RECQL4.[5][6][7]
Kratke činjenice Dostupne strukture, PDB ...
Zatvori
Dužina 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 |
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]
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.
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. 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.
- 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.
