DNA excision repair protein ERCC-8 is a
protein that in humans is encoded by the ERCC8gene.[5][6]
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.[6]
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.[7] Mutations in the CSA gene account for about 20% of CS cases.[8]
Function
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.[9] Within the cell, the CSA protein localizes to sites of
DNA damage, particularly
inter-strand cross-links, double-strand breaks and some mono-adducts.[7]
^"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.
^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.