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DNA repair protein complementing XP-G cells is a protein that in humans is encoded by the ERCC5gene.[1][2]
Excision repair cross-complementing rodent repair deficiency, complementation group 5 (xeroderma pigmentosum, complementation group G) is involved in excision repair of UV-induced DNA damage. Mutations cause Cockayne syndrome, which is characterized by severe growth defects, mental retardation, and cachexia. Multiple alternatively spliced transcript variants encoding distinct isoforms have been described, but the biological validity of all variants has not been determined.[2]
Mutational defects in the Ercc5(Xpg) gene can cause either the cancer-prone condition xeroderma pigmentosum (XP) alone, or in combination with the severe neurodevelopmental disorder Cockayne syndrome (CS) or the infantile lethal cerebro-oculo-facio-skeletal syndrome.[4]
Mouse model
An Ercc5(Xpg) mutant mouse model presented features of premature aging including cachexia and osteoporosis with pronounced degenerative phenotypes in both liver and brain.[4] These mutant mice developed a multi-system premature aging degenerative phenotype that appears to strengthen the link between DNA damage and aging.[4] (see DNA damage theory of aging).
Dietary restriction, which extends lifespan of wild-type mice, also substantially increased the lifespan of Ercc5(Xpg) mutant mice.[5] Dietary restriction of the mutant mice, while delaying aging, also appeared to slow the accumulation of genome wide DNA damage and to preserve transcriptional output, thus contributing to improved cell viability.
↑Samec S, Jones TA, Corlet J, Scherly D, Sheer D, Wood RD, Clarkson SG (Oct 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. PMID8088806.
↑Drury, S; Boustred, C; Tekman, M; Stanescu, H; Kleta, R; Lench, N; Chitty, L. S.; Scott, R. H. (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. 164 (7): 1777–83. doi:10.1002/ajmg.a.36506. PMID24700531.
↑Iyer, N; Reagan M S; Wu K J; Canagarajah B; Friedberg E C (Feb 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. UNITED STATES. 35 (7): 2157–67. doi:10.1021/bi9524124. ISSN0006-2960. PMID8652557.
Takahashi E, Shiomi N, Shiomi T (1993). "Precise localization of the excision repair gene, ERCC5, to human chromosome 13q32.3-q33.1 by direct R-banding fluorescence in situ hybridization". Jpn. J. Cancer Res. 83 (11): 1117–9. doi:10.1111/j.1349-7006.1992.tb02731.x. PMID1483924.
Mudgett JS, MacInnes MA (1991). "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. PMID2276736.
Shiomi T, Harada Y, Saito T, et al. (1994). "An ERCC5 gene with homology to yeast RAD2 is involved in group G xeroderma pigmentosum". Mutat. Res. 314 (2): 167–75. doi:10.1016/0921-8777(94)90080-9. PMID7510366.
Cloud KG, Shen B, Strniste GF, Park MS (1995). "XPG protein has a structure-specific endonuclease activity". Mutat. Res. 347 (2): 55–60. doi:10.1016/0165-7992(95)90070-5. PMID7651464.
Matsunaga T, Mu D, Park CH, et al. (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". J. Biol. Chem. 270 (35): 20862–9. doi:10.1074/jbc.270.35.20862. PMID7657672.
Nouspikel T, Clarkson SG (1994). "Mutations that disable the DNA repair gene XPG in a xeroderma pigmentosum group G patient". Hum. Mol. Genet. 3 (6): 963–7. doi:10.1093/hmg/3.6.963. PMID7951246.
O'Donovan A, Scherly D, Clarkson SG, Wood RD (1994). "Isolation of active recombinant XPG protein, a human DNA repair endonuclease". J. Biol. Chem. 269 (23): 15965–8. PMID8206890.
Scherly D, Nouspikel T, Corlet J, et al. (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. PMID8483504.
Iyer N, Reagan MS, Wu KJ, et al. (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. PMID8652557.
Cooper PK, Nouspikel T, Clarkson SG, Leadon SA (1997). "Defective transcription-coupled repair of oxidative base damage in Cockayne syndrome patients from XP group G". Science. 275 (5302): 990–3. doi:10.1126/science.275.5302.990. PMID9020084. (Retracted. If this is an intentional citation to a retracted paper, please replace {{Retracted}} with {{Retracted|intentional=yes}}.)