Excision repair cross-complementation group 6 (ERCC6) (ERCC6)

Excision repair cross-complementation group 6 (ERCC6), also known as Cockayne syndrome protein B (CSB), is an ATP-dependent DNA helicase and a member of the SWI/SNF family of chromatin remodeling proteins [UniProt, NCBI]. It serves as a master scaffold for transcription-coupled nucleotide excision repair (TC-NER), a specialized pathway that prioritizes the repair of DNA lesions that stall RNA polymerase II [PubMed: 31515460]. Beyond its role in DNA repair, ERCC6 is involved in regulating ribosomal RNA synthesis, maintaining mitochondrial DNA integrity, and modulating the cellular response to oxidative stress [PubMed: 25605872]. Mutations in ERCC6 are the primary cause of Cockayne syndrome type B, a severe multisystem disorder characterized by microcephaly, growth failure, and premature aging [NIH MedlinePlus]. In oncology, ERCC6 is frequently upregulated in various malignancies, including lung and prostate cancers, where it promotes tumor cell survival and resistance to DNA-damaging therapies like cisplatin [PubMed: 25605872]. While no FDA-approved drugs currently target ERCC6, it is an active area of research for developing sensitizing agents to overcome chemoresistance in cancer [PubMed: 31515460]. Therapeutic challenges include the potential for systemic toxicity, as inhibiting ERCC6 could induce phenotypes similar to Cockayne syndrome in healthy tissues [PubMed: 26365159].

Other names

Cockayne syndrome protein BCSBDNA excision repair protein ERCC-6ATP-dependent helicase ERCC6CKN2PIG24

Inhibition of transcription-coupled nucleotide excision repair (TC-NER) to sensitize cells to DNA-damaging agents.