Biology:ERCC5

Short description: Protein-coding gene in the species Homo sapiens

Generic protein structure example

DNA repair protein complementing XP-G cells is a protein that in humans is encoded by the ERCC5 gene.

Function

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.

Mutations in ERCC5 cause arthrogryposis.

XPG is a structure specific endonuclease that incises DNA at the 3’ side of the damaged nucleotide during nucleotide excision repair.

Syndromes

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.

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. These mutant mice developed a multi-system premature aging degenerative phenotype that appears to strengthen the link between DNA damage and aging. (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. 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.

Interactions

ERCC5 has been shown to interact with ERCC2.

External links

• GeneReviews/NIH/NCBI/UW entry on Xeroderma Pigmentosum

Further reading

• "Detection of chromatin-bound PCNA in mammalian cells and its use to study DNA excision repair". Journal of Radiation Research 40 (1): 1–12. March 1999. doi:10.1269/jrr.40.1. PMID 10408173. Bibcode: 1999JRadR..40....1M. http://pdfs.semanticscholar.org/e6ea/6b981f9bbf61fb2052664cdda64ba54a1d59.pdf. 
• "A summary of mutations in the UV-sensitive disorders: xeroderma pigmentosum, Cockayne syndrome, and trichothiodystrophy". Human Mutation 14 (1): 9–22. 1999. doi:10.1002/(SICI)1098-1004(1999)14:1<9::AID-HUMU2>3.0.CO;2-6. PMID 10447254. 
• "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. November 1992. doi:10.1111/j.1349-7006.1992.tb02731.x. PMID 1483924. 
• "Isolation of the functional human excision repair gene ERCC5 by intercosmid recombination". Genomics 8 (4): 623–33. December 1990. doi:10.1016/0888-7543(90)90248-S. PMID 2276736. https://zenodo.org/record/1258575. 
• "An ERCC5 gene with homology to yeast RAD2 is involved in group G xeroderma pigmentosum". Mutation Research 314 (2): 167–75. March 1994. doi:10.1016/0921-8777(94)90080-9. PMID 7510366. 
• "Nomenclature of human DNA repair genes". Mutation Research 315 (1): 41–2. July 1994. doi:10.1016/0921-8777(94)90026-4. PMID 7517009. 
• "XPG protein has a structure-specific endonuclease activity". Mutation Research 347 (2): 55–60. July 1995. doi:10.1016/0165-7992(95)90070-5. PMID 7651464. https://zenodo.org/record/1258361. 
• "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. September 1995. doi:10.1074/jbc.270.35.20862. PMID 7657672. 
• "Mutations that disable the DNA repair gene XPG in a xeroderma pigmentosum group G patient". Human Molecular Genetics 3 (6): 963–7. June 1994. doi:10.1093/hmg/3.6.963. PMID 7951246. http://doc.rero.ch/record/292968/files/3-6-963.pdf. 
• "Human xeroderma pigmentosum group G gene encodes a DNA endonuclease". Nucleic Acids Research 22 (16): 3312–6. August 1994. doi:10.1093/nar/22.16.3312. PMID 8078765. 
• "XPG endonuclease makes the 3' incision in human DNA nucleotide excision repair". Nature 371 (6496): 432–5. September 1994. doi:10.1038/371432a0. PMID 8090225. Bibcode: 1994Natur.371..432O. 
• "Isolation of active recombinant XPG protein, a human DNA repair endonuclease". The Journal of Biological Chemistry 269 (23): 15965–8. June 1994. doi:10.1016/S0021-9258(17)33956-X. PMID 8206890. 
• "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. October 1993. doi:10.1128/MCB.13.10.6393. PMID 8413238. 
• "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. May 1993. doi:10.1038/363182a0. PMID 8483504. Bibcode: 1993Natur.363..182S. 
• "Identical defects in DNA repair in xeroderma pigmentosum group G and rodent ERCC group 5". Nature 363 (6425): 185–8. May 1993. doi:10.1038/363185a0. PMID 8483505. Bibcode: 1993Natur.363..185O. 
• "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. February 1996. doi:10.1021/bi9524124. PMID 8652557. 
• "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. August 1996. doi:10.1073/pnas.93.16.8368. PMID 8710877. Bibcode: 1996PNAS...93.8368P.