ERCC5
(Preusmjereno sa XPG)
Komplementarni protein za popravak DNK XP-G ćelija jest protein koji je kod ljudi kodiran genom ERCC5 sa hromosoma 13.[5][6]
Aminokiselinska sekvenca
urediDužina polipeptidnog lanca je 1.186 aminokiselina, a molekulska težina 133.108 Da.[6]
| 10 | 20 | 30 | 40 | 50 | ||||
|---|---|---|---|---|---|---|---|---|
| MGVQGLWKLL | ECSGRQVSPE | ALEGKILAVD | ISIWLNQALK | GVRDRHGNSI | ||||
| ENPHLLTLFH | RLCKLLFFRI | RPIFVFDGDA | PLLKKQTLVK | RRQRKDLASS | ||||
| DSRKTTEKLL | KTFLKRQAIK | TAFRSKRDEA | LPSLTQVRRE | NDLYVLPPLQ | ||||
| EEEKHSSEEE | DEKEWQERMN | QKQALQEEFF | HNPQAIDIES | EDFSSLPPEV | ||||
| KHEILTDMKE | FTKRRRTLFE | AMPEESDDFS | QYQLKGLLKK | NYLNQHIEHV | ||||
| QKEMNQQHSG | HIRRQYEDEG | GFLKEVESRR | VVSEDTSHYI | LIKGIQAKTV | ||||
| AEVDSESLPS | SSKMHGMSFD | VKSSPCEKLK | TEKEPDATPP | SPRTLLAMQA | ||||
| ALLGSSSEEE | LESENRRQAR | GRNAPAAVDE | GSISPRTLSA | IKRALDDDED | ||||
| VKVCAGDDVQ | TGGPGAEEMR | INSSTENSDE | GLKVRDGKGI | PFTATLASSS | ||||
| VNSAEEHVAS | TNEGREPTDS | VPKEQMSLVH | VGTEAFPISD | ESMIKDRKDR | ||||
| LPLESAVVRH | SDAPGLPNGR | ELTPASPTCT | NSVSKNETHA | EVLEQQNELC | ||||
| PYESKFDSSL | LSSDDETKCK | PNSASEVIGP | VSLQETSSIV | SVPSEAVDNV | ||||
| ENVVSFNAKE | HENFLETIQE | QQTTESAGQD | LISIPKAVEP | MEIDSEESES | ||||
| DGSFIEVQSV | ISDEELQAEF | PETSKPPSEQ | GEEELVGTRE | GEAPAESESL | ||||
| LRDNSERDDV | DGEPQEAEKD | AEDSLHEWQD | INLEELETLE | SNLLAQQNSL | ||||
| KAQKQQQERI | AATVTGQMFL | ESQELLRLFG | IPYIQAPMEA | EAQCAILDLT | ||||
| DQTSGTITDD | SDIWLFGARH | VYRNFFNKNK | FVEYYQYVDF | HNQLGLDRNK | ||||
| LINLAYLLGS | DYTEGIPTVG | CVTAMEILNE | FPGHGLEPLL | KFSEWWHEAQ | ||||
| KNPKIRPNPH | DTKVKKKLRT | LQLTPGFPNP | AVAEAYLKPV | VDDSKGSFLW | ||||
| GKPDLDKIRE | FCQRYFGWNR | TKTDESLFPV | LKQLDAQQTQ | LRIDSFFRLA | ||||
| QQEKEDAKRI | KSQRLNRAVT | CMLRKEKEAA | ASEIEAVSVA | MEKEFELLDK | ||||
| AKGKTQKRGI | TNTLEESSSL | KRKRLSDSKG | KNTCGGFLGE | TCLSESSDGS | ||||
| SSEDAESSSL | MNVQRRTAAK | EPKTSASDSQ | NSVKEAPVKN | GGATTSSSSD | ||||
| SDDDGGKEKM | VLVTARSVFG | KKRRKLRRAR | GRKRKT |
Funkcija
urediEkscizijska popravka unakrsne komplementarne reparacije glodara, komplementacijska grupa 5 (xeroderma pigmentosum, komplementacijska grupa G) uključena je u ekscizijsku popravku oštećenja DNK izazvane UV zračenjem. Mutacije uzrokuju Cockayneov sindrom, koji se karakterizira teškim defektima rasta, mentalnom retardacijom i kaheksijom. Opisano je više alternativno prerađenih varijanti transkripta koje kodiraju različite izoforme, ali biološka valjanost svih varijanti nije utvrđena.[6]
Mutacije u ERCC5 uzrokuju artrogripozu.[7]
XPG je strukturno specifična endonukleaza koja urezuje DNK na 3’ strani oštećenog nukleotida tokom reparacije ekscizijom nukleotida.
Sindromi
urediMutacijski defekti gena Ercc5(Xpg) mogu uzrokovati stanje sklono karcinomu xeroderma pigmentosum (XP) samostalno ili u kombinaciji s teškim neurorazvojnim poremećajem Cockayneov sindrom (CS) ili infantilnim smrtonosnim cerebro-okulo-facio-skeletnim sindromom.[8]
Model miša
urediModel mutantnog miša Ercc5(Xpg) predstavio je karakteristike preranog starenja, uključujući kaheksiju i osteoporozu sa izraženim degenerativnim fenotipovima u jetri i mozgu.[8] Ovi mutirani miševi su razvili multisistemski degenerativni fenotip preranog starenja koji izgleda jača vezu između oštećenja DNK i starenja.[8] (vidi Teorija oštećenja DNK starenjem).
Ograničenje u ishrani, koje produžava životni vijek miševa divljeg tipa, također je značajno produžilo životni vijek Ercc5(Xpg) mutantnih miševa.[9] Ograničenje ishrane mutantnih miševa, dok je odlagalo starenje, također je usporilo akumulaciju oštećenja DNK u čitavom genomu i očuvalo transkripcioni izlaz, doprinoseći tako poboljšanoj vitalnosti ćelija.
Interakcije
urediPokazalo se da ERCC5 u interakciji sa ERCC2.[10]
Reference
uredi- ^ a b c GRCh38: Ensembl release 89: ENSG00000134899 - Ensembl, maj 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000026048 - 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.
- ^ Samec S, Jones TA, Corlet J, Scherly D, Sheer D, Wood RD, Clarkson SG (maj 1994). "The human gene for xeroderma pigmentosum complementation group G (XPG) maps to 13q33 by fluorescence in situ hybridization". Genomics. 21 (1): 283–5. doi:10.1006/geno.1994.1261. PMID 8088806.
- ^ a b c "Entrez Gene: ERCC5 excision repair cross-complementing rodent repair deficiency, complementation group 5 (xeroderma pigmentosum, complementation group G (Cockayne syndrome))".
- ^ Drury S, Boustred C, Tekman M, Stanescu H, Kleta R, Lench N, Chitty LS, Scott RH (juli 2014). "A novel homozygous ERCC5 truncating mutation in a family with prenatal arthrogryposis--further evidence of genotype-phenotype correlation". American Journal of Medical Genetics. Part A. 164A (7): 1777–83. doi:10.1002/ajmg.a.36506. PMID 24700531. S2CID 8023991.
- ^ a b c Barnhoorn S, Uittenboogaard LM, Jaarsma D, Vermeij WP, Tresini M, Weymaere M, Menoni H, Brandt RM, de Waard MC, Botter SM, Sarker AH, Jaspers NG, van der Horst GT, Cooper PK, Hoeijmakers JH, van der Pluijm I (oktobar 2014). "Cell-autonomous progeroid changes in conditional mouse models for repair endonuclease XPG deficiency". PLOS Genetics. 10 (10): e1004686. doi:10.1371/journal.pgen.1004686. PMC 4191938. PMID 25299392.
- ^ Vermeij WP, Dollé ME, Reiling E, Jaarsma D, Payan-Gomez C, Bombardieri CR, Wu H, Roks AJ, Botter SM, van der Eerden BC, Youssef SA, Kuiper RV, Nagarajah B, van Oostrom CT, Brandt RM, Barnhoorn S, Imholz S, Pennings JL, de Bruin A, Gyenis Á, Pothof J, Vijg J, van Steeg H, Hoeijmakers JH (septembar 2016). "Restricted diet delays accelerated ageing and genomic stress in DNA-repair-deficient mice". Nature. 537 (7620): 427–431. Bibcode:2016Natur.537..427V. doi:10.1038/nature19329. PMC 5161687. PMID 27556946.
- ^ Iyer N, Reagan MS, Wu KJ, Canagarajah B, Friedberg EC (februar 1996). "Interactions involving the human RNA polymerase II transcription/nucleotide excision repair complex TFIIH, the nucleotide excision repair protein XPG, and Cockayne syndrome group B (CSB) protein". Biochemistry. 35 (7): 2157–67. doi:10.1021/bi9524124. PMID 8652557.
Dopunska literatura
uredi- Miura M (mart 1999). "Detection of chromatin-bound PCNA in mammalian cells and its use to study DNA excision repair". Journal of Radiation Research. 40 (1): 1–12. Bibcode:1999JRadR..40....1M. doi:10.1269/jrr.40.1. PMID 10408173.
- Cleaver JE, Thompson LH, Richardson AS, States JC (1999). "A summary of mutations in the UV-sensitive disorders: xeroderma pigmentosum, Cockayne syndrome, and trichothiodystrophy". Human Mutation. 14 (1): 9–22. doi:10.1002/(SICI)1098-1004(1999)14:1<9::AID-HUMU2>3.0.CO;2-6. PMID 10447254. S2CID 24148589.
- Takahashi E, Shiomi N, Shiomi T (novembar 1992). "Precise localization of the excision repair gene, ERCC5, to human chromosome 13q32.3-q33.1 by direct R-banding fluorescence in situ hybridization". Japanese Journal of Cancer Research. 83 (11): 1117–9. doi:10.1111/j.1349-7006.1992.tb02731.x. PMC 5918714. PMID 1483924.
- Mudgett JS, MacInnes MA (decembar 1990). "Isolation of the functional human excision repair gene ERCC5 by intercosmid recombination". Genomics. 8 (4): 623–33. doi:10.1016/0888-7543(90)90248-S. PMID 2276736.
- Shiomi T, Harada Y, Saito T, Shiomi N, Okuno Y, Yamaizumi M (mart 1994). "An ERCC5 gene with homology to yeast RAD2 is involved in group G xeroderma pigmentosum". Mutation Research. 314 (2): 167–75. doi:10.1016/0921-8777(94)90080-9. PMID 7510366.
- Lehmann AR, Bootsma D, Clarkson SG, Cleaver JE, McAlpine PJ, Tanaka K, Thompson LH, Wood RD (juli 1994). "Nomenclature of human DNA repair genes". Mutation Research. 315 (1): 41–2. doi:10.1016/0921-8777(94)90026-4. PMID 7517009.
- Cloud KG, Shen B, Strniste GF, Park MS (juli 1995). "XPG protein has a structure-specific endonuclease activity". Mutation Research. 347 (2): 55–60. doi:10.1016/0165-7992(95)90070-5. PMID 7651464.
- Matsunaga T, Mu D, Park CH, Reardon JT, Sancar A (septembar 1995). "Human DNA repair excision nuclease. Analysis of the roles of the subunits involved in dual incisions by using anti-XPG and anti-ERCC1 antibodies". The Journal of Biological Chemistry. 270 (35): 20862–9. doi:10.1074/jbc.270.35.20862. PMID 7657672.
- Nouspikel T, Clarkson SG (juni 1994). "Mutations that disable the DNA repair gene XPG in a xeroderma pigmentosum group G patient" (PDF). Human Molecular Genetics. 3 (6): 963–7. doi:10.1093/hmg/3.6.963. PMID 7951246.
- Habraken Y, Sung P, Prakash L, Prakash S (august 1994). "Human xeroderma pigmentosum group G gene encodes a DNA endonuclease". Nucleic Acids Research. 22 (16): 3312–6. doi:10.1093/nar/22.16.3312. PMC 523723. PMID 8078765.
- O'Donovan A, Davies AA, Moggs JG, West SC, Wood RD (septembar 1994). "XPG endonuclease makes the 3' incision in human DNA nucleotide excision repair". Nature. 371 (6496): 432–5. Bibcode:1994Natur.371..432O. doi:10.1038/371432a0. PMID 8090225. S2CID 4328388.
- O'Donovan A, Scherly D, Clarkson SG, Wood RD (juni 1994). "Isolation of active recombinant XPG protein, a human DNA repair endonuclease". The Journal of Biological Chemistry. 269 (23): 15965–8. doi:10.1016/S0021-9258(17)33956-X. PMID 8206890.
- MacInnes MA, Dickson JA, Hernandez RR, Learmonth D, Lin GY, Mudgett JS, Park MS, Schauer S, Reynolds RJ, Strniste GF (oktobar 1993). "Human ERCC5 cDNA-cosmid complementation for excision repair and bipartite amino acid domains conserved with RAD proteins of Saccharomyces cerevisiae and Schizosaccharomyces pombe". Molecular and Cellular Biology. 13 (10): 6393–402. doi:10.1128/MCB.13.10.6393. PMC 364698. PMID 8413238.
- Scherly D, Nouspikel T, Corlet J, Ucla C, Bairoch A, Clarkson SG (maj 1993). "Complementation of the DNA repair defect in xeroderma pigmentosum group G cells by a human cDNA related to yeast RAD2". Nature. 363 (6425): 182–5. Bibcode:1993Natur.363..182S. doi:10.1038/363182a0. PMID 8483504. S2CID 9713824.
- O'Donovan A, Wood RD (maj 1993). "Identical defects in DNA repair in xeroderma pigmentosum group G and rodent ERCC group 5". Nature. 363 (6425): 185–8. Bibcode:1993Natur.363..185O. doi:10.1038/363185a0. PMID 8483505. S2CID 4372167.
- Iyer N, Reagan MS, Wu KJ, Canagarajah B, Friedberg EC (februar 1996). "Interactions involving the human RNA polymerase II transcription/nucleotide excision repair complex TFIIH, the nucleotide excision repair protein XPG, and Cockayne syndrome group B (CSB) protein". Biochemistry. 35 (7): 2157–67. doi:10.1021/bi9524124. PMID 8652557.
- Park MS, Knauf JA, Pendergrass SH, Coulon CH, Strniste GF, Marrone BL, MacInnes MA (august 1996). "Ultraviolet-induced movement of the human DNA repair protein, Xeroderma pigmentosum type G, in the nucleus". Proceedings of the National Academy of Sciences of the United States of America. 93 (16): 8368–73. Bibcode:1996PNAS...93.8368P. doi:10.1073/pnas.93.16.8368. PMC 38677. PMID 8710877.