ERCC8 : ERCC excision repair 8, CSA ubiquitin ligase complex subunit
Description
The ERCC8 (ERCC excision repair 8, CSA ubiquitin ligase complex subunit) is a protein-coding gene located on chromosome 5.
The ERCC8 gene provides instructions for making a protein called Cockayne syndrome A (CSA), which is involved in repairing damaged DNA. DNA damage can be caused by various agents like UV rays, toxic chemicals, radiation, and free radicals. This damage can obstruct crucial cell processes, such as gene transcription, the first step in protein production. If left unrepaired, DNA damage accumulates, leading to cell dysfunction and even death. Despite frequent occurrences of DNA damage, cells usually have mechanisms to fix it before it causes problems. One such mechanism involves the CSA protein, which specializes in repairing damaged DNA within active genes. The exact role of CSA in this repair process is still unclear, but it interacts with other proteins to identify damaged DNA regions.
The ERCC8 protein is a substrate-recognition component of the CSA complex, a DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex that is involved in transcription-coupled nucleotide excision repair. The CSA 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. ERCC8 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. It also plays a role in DNA single-strand and double-strand breaks (DSSBs) repair, specifically in the repair of DSSBs by non-homologous end joining (NHEJ).
ERCC8 is also known as CKN1, CSA, UVSS2.
Associated Diseases
- UV-sensitive syndrome 2
- Cockayne syndrome type 2
- Cockayne syndrome type 1
- Cockayne syndrome type 3
- Cockayne syndrome, type A
- Cockayne syndrome
- UV-sensitive syndrome
