Hierarchical mechanisms control the clearance of DNA lesion-stalled RNA polymerase II.

ABSTRACT: Stalling of elongating RNA polymerase II (RNAPII) at DNA lesions blocks transcription and triggers transcription-coupled repair (TCR). However, the mechanisms determining the fate of stalled RNAPII remain incompletely understood. Here, we develop a time-resolved assay to track RNAPII clearance and degradation at UV-induced lesions. We show that RNAPII ubiquitylation by CSB and the CRL4^CSA ubiquitin ligase is essential, as loss of these proteins causes persistent RNAPII accumulation at damage sites. Downstream of CSB/CRL4^CSA-mediated ubiquitylation, two distinct pathways mediate RNAPII removal. The primary rapid route relies on TFIIH, with its XPD helicase activity driving RNAPII dissociation after proper recruitment and positioning by ELOF1, UVSSA, and STK19. A second

SUBMITTER: van der Meer PJ 

PROVIDER: S-EPMC12904859 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature