ERCC5

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.

References

References

1. (May 1994). "The human gene for xeroderma pigmentosum complementation group G (XPG) maps to 13q33 by fluorescence in situ hybridization". Genomics.
2. "Entrez Gene: ERCC5 excision repair cross-complementing rodent repair deficiency, complementation group 5 (xeroderma pigmentosum, complementation group G (Cockayne syndrome))".
3. (July 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.
4. (October 2014). "Cell-autonomous progeroid changes in conditional mouse models for repair endonuclease XPG deficiency". PLOS Genetics.
5. (September 2016). "Restricted diet delays accelerated ageing and genomic stress in DNA-repair-deficient mice". Nature.
6. (February 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.