ERCC8

This gene encodes a WD repeat protein, which interacts with Cockayne syndrome type B (CSB) protein and with p44 protein, a subunit of the RNA polymerase II transcription factor IIH. Mutations in this gene have been identified in patients with hereditary disease Cockayne syndrome (CS). CS cells are abnormally sensitive to ultraviolet radiation and are defective in the repair of transcriptionally active genes. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2014]

ERCC Excision Repair 8, CSA Ubiquitin Ligase Complex Subunit

Substrate-recognition component of the CSA complex, a DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex, involved in transcription-coupled nucleotide excision repair. The CSA complex (DCX(ERCC8) complex) promotes the ubiquitination and subsequent proteasomal degradation of ERCC6 in a UV-dependent manner; ERCC6 degradation is essential for the recovery of RNA synthesis after transcription-coupled repair. It is required for the recruitment of XAB2, HMGN1 and TCEA1/TFIIS to a transcription-coupled repair complex which removes RNA polymerase II-blocking lesions from the transcribed strand of active genes. Plays a role in DNA single-strand and double-strand breaks (DSSBs) repair; involved in repair of DSSBs by non-homologous end joining (NHEJ) (PubMed:29545921).

Cellular response to DNA damage stimulus Source: UniProtKB
DNA duplex unwinding Source: GOC
Double-strand break repair via classical nonhomologous end joining Source: UniProtKB
Nucleotide-excision repair Source: UniProtKB
Positive regulation of DNA repair Source: UniProtKB
Proteasome-mediated ubiquitin-dependent protein catabolic process Source: UniProtKB
Protein autoubiquitination Source: UniProtKB
Protein polyubiquitination Source: UniProtKB
Response to oxidative stress Source: UniProtKB
Response to UV Source: UniProtKB
Single strand break repair Source: UniProtKB
Transcription-coupled nucleotide-excision repair Source: MGI

Nucleus; Nucleus matrix. UV-induced translocation to the nuclear matrix is dependent on ERCC6.

Cockayne syndrome A (CSA):
A rare disorder characterized by cutaneous sensitivity to sunlight, abnormal and slow growth, cachectic dwarfism, progeroid appearance, progressive pigmentary retinopathy and sensorineural deafness. There is delayed neural development and severe progressive neurologic degeneration resulting in mental retardation. Two clinical forms are recognized: in the classical form or Cockayne syndrome type 1, the symptoms are progressive and typically become apparent within the first few years or life; the less common Cockayne syndrome type 2 is characterized by more severe symptoms that manifest prenatally. Cockayne syndrome shows some overlap with certain forms of xeroderma pigmentosum. Unlike xeroderma pigmentosum, patients with Cockayne syndrome do not manifest increased freckling and other pigmentation abnormalities in the skin and have no significant increase in skin cancer.
UV-sensitive syndrome 2 (UVSS2):
An autosomal recessive disorder characterized by cutaneous photosensitivity and mild freckling in the absence of neurological abnormalities or skin tumors.