ERCC5

This gene encodes a single-strand specific DNA endonuclease that makes the 3' incision in DNA excision repair following UV-induced damage. The protein may also function in other cellular processes, including RNA polymerase II transcription, and transcription-coupled DNA repair. Mutations in this gene cause xeroderma pigmentosum complementation group G (XP-G), which is also referred to as xeroderma pigmentosum VII (XP7), a skin disorder characterized by hypersensitivity to UV light and increased susceptibility for skin cancer development following UV exposure. Some patients also develop Cockayne syndrome, which is characterized by severe growth defects, cognitive disability, and cachexia. Read-through transcription exists between this gene and the neighboring upstream BIVM (basic, immunoglobulin-like variable motif containing) gene. [provided by RefSeq, Feb 2011]

ERCC Excision Repair 5, Endonuclease

Single-stranded structure-specific DNA endonuclease involved in DNA excision repair (PubMed:8206890, PubMed:8090225, PubMed:8078765, PubMed:7651464, PubMed:32821917, PubMed:32522879).

Makes the 3'incision in DNA nucleotide excision repair (NER) (PubMed:8090225, PubMed:8078765, PubMed:32821917, PubMed:32522879).

Binds and bends DNA repair bubble substrate and breaks base stacking at the single-strand/double-strand DNA junction of the DNA bubble (PubMed:32522879).

Plays a role in base excision repair (BER) by promoting the binding of DNA glycosylase NTHL1 to its substrate and increasing NTHL1 catalytic activity that removes oxidized pyrimidines from DNA (PubMed:9927729).

Involved in transcription-coupled nucleotide excision repair (TCR) which allows RNA polymerase II-blocking lesions to be rapidly removed from the transcribed strand of active genes (PubMed:16246722).

Functions during the initial step of TCR in cooperation with ERCC6/CSB to recognized stalled RNA polymerase II (PubMed:16246722).

Also, stimulates ERCC6/CSB binding to the DNA repair bubble and ERCC6/CSB ATPase activity (PubMed:16246722).

Required for DNA replication fork maintenance and preservation of genomic stability (PubMed:26833090, PubMed:32522879).

Involved in homologous recombination repair (HRR) induced by DNA replication stress by recruiting RAD51, BRCA2, and PALB2 to the damaged DNA site (PubMed:26833090).

During HRR, binds to the replication fork with high specificity and stabilizes it (PubMed:32522879).

Also, acts upstream of HRR, to promote the release of BRCA1 from DNA (PubMed:26833090).

Base-excision repair, AP site formation Source: UniProtKB
Double-strand break repair via homologous recombination Source: UniProtKB
Negative regulation of apoptotic process Source: UniProtKB
Nucleotide-excision repair Source: UniProtKB
Nucleotide-excision repair, DNA incision, 3'-to lesion Source: UniProtKB
Nucleotide-excision repair, DNA incision, 5'-to lesion Source: Reactome
Regulation of catalytic activity Source: UniProtKB
Response to UV Source: UniProtKB
Response to UV-C Source: UniProtKB
Transcription-coupled nucleotide-excision repair Source: UniProtKB
UV protection Source: MGI

Nucleus; Chromosome. Colocalizes with RAD51 to nuclear foci in S phase (PubMed:26833090). Localizes to DNA double-strand breaks (DBS) during replication stress (PubMed:26833090). Colocalizes with BRCA2 to nuclear foci following DNA replication stress (PubMed:26833090).

Xeroderma pigmentosum complementation group G (XP-G):
An autosomal recessive pigmentary skin disorder characterized by solar hypersensitivity of the skin, high predisposition for developing cancers on areas exposed to sunlight and, in some cases, neurological abnormalities. The skin develops marked freckling and other pigmentation abnormalities. Some XP-G patients present features of Cockayne syndrome, cachectic dwarfism, pigmentary retinopathy, ataxia, decreased nerve conduction velocities. The phenotype combining xeroderma pigmentosum and Cockayne syndrome traits is referred to as XP-CS complex.
Cerebro-oculo-facio-skeletal syndrome 3 (COFS3):
A disorder of prenatal onset characterized by microcephaly, congenital cataracts, facial dysmorphism, neurogenic arthrogryposis, growth failure and severe psychomotor retardation. COFS is considered to be part of the nucleotide-excision repair disorders spectrum that include also xeroderma pigmentosum, trichothiodystrophy and Cockayne syndrome.