ERCC6

ERCC6 is a human gene that encodes the Cockayne syndrome protein B (CSB). CSB is a large, ATP-dependent DNA helicase-like protein and a member of the SWI/SNF2 family of chromatin remodelers. The protein plays a central role in transcription-coupled nucleotide excision repair (TC-NER), a subpathway of NER that prioritizes lesions on actively transcribed genes.

In TC-NER, CSB recognizes DNA damage within transcribed regions and coordinates the recruitment of repair factors to the site of the lesion. It collaborates with the CSA protein, encoded by ERCC8, and interacts with RNA polymerase II to facilitate damage recognition, chromatin remodeling, and restoration of transcription after repair. Beyond TC-NER, CSB is also implicated in broader transcription regulation and chromatin remodeling activities and may influence cellular responses to oxidative stress.

Mutations in ERCC6 cause Cockayne syndrome type B (CS-B), an autosomal recessive neurodegenerative disorder characterized by growth retardation, photosensitivity, progressive neurologic deterioration, sensorineural deafness, cataracts, and premature aging. Disease severity varies among individuals, and CS-B is part of a spectrum that includes Cockayne syndrome type A, caused by mutations in ERCC8. ERCC6 mutations disrupt TC-NER and related chromatin remodeling functions, contributing to genome instability and the clinical features of the syndrome.

ERCC6 is broadly expressed and encodes a protein that integrates DNA repair with transcriptional control and chromatin dynamics. Ongoing research continues to refine genotype–phenotype relationships and explore potential therapeutic approaches for CS-B and related repair disorders.