Excision repair cross-complementing rodent repair deficiency complementation group 5 - Cockayne syndrome type A - Cockayne syndrome type B - DNA-directed RNA polymerase II complex (ERCC5-CSA/CSB-Pol II)

The Excision repair cross-complementing rodent repair deficiency complementation group 5 (ERCC5) - Cockayne syndrome type A/B (CSA/CSB) - DNA-directed RNA polymerase II complex is a fundamental functional unit of the transcription-coupled nucleotide excision repair (TC-NER) pathway (UniProt P28715, Q13516, Q03468). TC-NER is a specialized DNA repair mechanism that prioritizes the removal of bulky, helix-distorting lesions from the template strands of actively transcribed genes to prevent transcriptional arrest (PubMed 9372911). The process is initiated when DNA-directed RNA polymerase II stalls at a lesion, which then recruits the CSB (ERCC6) protein to remodel chromatin and the CSA (ERCC8) protein as part of an E3 ubiquitin ligase complex (Reactome R-HSA-6781827). These factors subsequently recruit the core NER machinery, including the structure-specific endonuclease ERCC5 (XPG), which performs the 3' incision of the damaged DNA strand (PubMed 16246722). Mutations in the components of this complex lead to severe genetic disorders such as Cockayne syndrome and Xeroderma pigmentosum group G, characterized by growth failure, neurodegeneration, and extreme sensitivity to ultraviolet radiation (PubMed 35248096). In oncology, this complex is a significant therapeutic target; its inhibition can sensitize cancer cells to platinum-based chemotherapies like cisplatin by preventing the repair of drug-induced DNA adducts (PubMed 38495341). Furthermore, the efficacy of the minor-groove binding drug trabectedin is dependent on the presence of functional ERCC5, which processes the drug-DNA complex into lethal double-strand breaks (PubMed 22118460).

Other names

XPG-CSA-CSB-Pol II complexTranscription-coupled nucleotide excision repair complexTC-NER complexERCC5-ERCC8-ERCC6-Pol II complexTranscription-coupled repair complex

Inhibition of transcription-coupled nucleotide excision repair (TC-NER) to sensitize cells to DNA-damaging agents; induction of DNA double-strand breaks via XPG-mediated processing of drug-DNA adducts.