ERCC8
Function
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 (PubMed:16751180, PubMed:16964240). 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 (PubMed:16751180). 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).
Involvement in disease
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 intellectual disability. 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.
None
The disease is caused by variants affecting the gene represented in this entry.
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.
None
The disease is caused by variants affecting the gene represented in this entry.
Pathway
Protein modification; protein ubiquitination.
Cellular localization
- Nucleus
- Nucleus matrix
- UV-induced translocation to the nuclear matrix is dependent on ERCC6.
Alternative names
CKN1, CSA, ERCC8, DNA excision repair protein ERCC-8, Cockayne syndrome WD repeat protein CSA