DNA excision repair protein ERCC-8 (ERCC8)

DNA excision repair protein ERCC-8 (ERCC8, CSA) is a WD-repeat protein that acts as a substrate-recognition component of the CSA ubiquitin ligase complex, crucial for transcription-coupled nucleotide excision repair (TC-NER), particularly removal of RNA polymerase II-blocking lesions in active genes[1][3][6]. Mutations in *ERCC8* cause Cockayne syndrome A, a rare, recessive neurodegenerative disorder presenting with developmental delay, photosensitivity, multi-system progressive degeneration, and accelerated aging[2][4][8]. ERCC8 is involved in DNA damage recognition, protein ubiquitination, and mediates the recovery of transcription following DNA repair, as well as regulation of ribosomal RNA synthesis through nucleolin interaction[4][6]. Disease mutations lead to deficient repair and clinical features most pronounced in the nervous system, skin, and growth[8].

Other names

Cockayne syndrome A protein (CSA)CKN1UVSS2Excision repair cross-complementation group 8Excision repair cross-complementing rodent repair deficiency, complementation group 8Cockayne syndrome WD repeat protein CSA

Drugs would theoretically modulate DNA repair, chromatin remodeling, or ubiquitin-proteasome degradation, but no specific drugs known to target ERCC8 directly[1][3][6].