DNA excision repair protein ERCC-8 is a protein that in humans is encoded by the ERCC8gene.[1][2]
This gene encodes a WD repeat protein, which interacts with the Cockayne syndrome type B (CSB) and p44 proteins, the latter being a subunit of the RNA polymerase II transcription factor II H. Mutations in this gene have been identified in patients with the hereditary disease Cockayne syndrome (CS). CS is an accelerated aging disorder characterized by photosensitivity, impaired development and multi-system progressive degeneration. The CS cells are abnormally sensitive to ultraviolet radiation and are defective in the repair of transcriptionally active genes. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene.[2]
CS arises from germlinemutations in either of two genesCSA(ERCC8) or CSB(ERCC6). CSA mutations generally give rise to a more moderate form of CS than CSB mutations.[3] Mutations in the CSA gene account for about 20% of CS cases.[4]
CSA and CSB proteins are thought to function in transcription and DNA repair, most notably in transcription-coupled nucleotide excision repair. CSA and CSB-deficient cells exhibit a lack of preferential repair of UV-induced cyclobutane pyrimidine dimers in actively transcribed genes, consistent with a failed transcription coupled nucleotide excision repair response.[5] Within the cell, the CSA protein localizes to sites of DNA damage, particularly inter-strand cross-links, double-strand breaks and some mono-adducts.[3]
↑Itoh T, Shiomi T, Shiomi N, Harada Y, Wakasugi M, Matsunaga T, Nikaido O, Friedberg EC, Yamaizumi M (April 1996). "Rodent complementation group 8 (ERCC8) corresponds to Cockayne syndrome complementation group A". Mutat Res. 362 (2): 167–74. doi:10.1016/0921-8777(95)00046-1. PMID8596535.
↑Nakatsu Y, Asahina H, Citterio E, Rademakers S, Vermeulen W, Kamiuchi S, Yeo JP, Khaw MC, Saijo M, Kodo N, Matsuda T, Hoeijmakers JH, Tanaka K (November 2000). "XAB2, a novel tetratricopeptide repeat protein involved in transcription-coupled DNA repair and transcription". J. Biol. Chem. UNITED STATES. 275 (45): 34931–7. doi:10.1074/jbc.M004936200. ISSN0021-9258. PMID10944529.
Henning KA, Li L, Iyer N, et al. (1995). "The Cockayne syndrome group A gene encodes a WD repeat protein that interacts with CSB protein and a subunit of RNA polymerase II TFIIH". Cell. 82 (4): 555–64. doi:10.1016/0092-8674(95)90028-4. PMID7664335.
Selby CP, Sancar A (1997). "Human transcription-repair coupling factor CSB/ERCC6 is a DNA-stimulated ATPase but is not a helicase and does not disrupt the ternary transcription complex of stalled RNA polymerase II". J. Biol. Chem. 272 (3): 1885–90. doi:10.1074/jbc.272.3.1885. PMID8999876.
Nakatsu Y, Asahina H, Citterio E, et al. (2001). "XAB2, a novel tetratricopeptide repeat protein involved in transcription-coupled DNA repair and transcription". J. Biol. Chem. 275 (45): 34931–7. doi:10.1074/jbc.M004936200. PMID10944529.
Groisman R, Polanowska J, Kuraoka I, et al. (2003). "The ubiquitin ligase activity in the DDB2 and CSA complexes is differentially regulated by the COP9 signalosome in response to DNA damage". Cell. 113 (3): 357–67. doi:10.1016/S0092-8674(03)00316-7. PMID12732143.
Cao H, Williams C, Carter M, Hegele RA (2004). "CKN1 (MIM 216400): mutations in Cockayne syndrome type A and a new common polymorphism". J. Hum. Genet. 49 (1): 61–3. doi:10.1007/s10038-003-0107-2. PMID14661080.
Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID14702039.
Ridley AJ, Colley J, Wynford-Thomas D, Jones CJ (2005). "Characterisation of novel mutations in Cockayne syndrome type A and xeroderma pigmentosum group C subjects". J. Hum. Genet. 50 (3): 151–4. doi:10.1007/s10038-004-0228-2. PMID15744458.
Sarker AH, Tsutakawa SE, Kostek S, et al. (2006). "Recognition of RNA polymerase II and transcription bubbles by XPG, CSB, and TFIIH: insights for transcription-coupled repair and Cockayne Syndrome". Mol. Cell. 20 (2): 187–98. doi:10.1016/j.molcel.2005.09.022. PMID16246722.
Fousteri M, Vermeulen W, van Zeeland AA, Mullenders LH (2006). "Cockayne syndrome A and B proteins differentially regulate recruitment of chromatin remodeling and repair factors to stalled RNA polymerase II in vivo". Mol. Cell. 23 (4): 471–82. doi:10.1016/j.molcel.2006.06.029. PMID16916636.
D'Errico M, Parlanti E, Teson M, et al. (2007). "The role of CSA in the response to oxidative DNA damage in human cells". Oncogene. 26 (30): 4336–43. doi:10.1038/sj.onc.1210232. PMID17297471.
