Structural basis of human transcription–DNA repair coupling

• DOI: 10.1038/s41586-021-03906-4
• Publication Date: 2021-09-15T16:03:19Z
• Authors: Goran Kokic; Felix R. Wagner; Aleksandar Chernev; Henning Urlaub; Patrick Cramer
• Keywords: Transcription; RNA polymerase II; Processivity; Cockayne syndrome

Abstract Transcription-coupled DNA repair removes bulky lesions from the genome 1,2 and protects cells against ultraviolet (UV) irradiation 3 . begins when RNA polymerase II (Pol II) stalls at a lesion recruits Cockayne syndrome protein CSB, E3 ubiquitin ligase, CRL4 CSA UV-stimulated scaffold A (UVSSA) Here we provide five high-resolution structures of Pol transcription complexes containing human transcription-coupled factors elongation PAF1 complex (PAF) SPT6. Together with biochemical published 3,4 data, model for transcription–repair coupling. Stalling triggers replacement factor DSIF by which binds to PAF moves upstream The resulting complex, EC TCR , uses CSA-stimulated translocase activity CSB pull on push forward. If cannot be bypassed, spans over clamp ubiquitylates RPB1 residue K1268, enabling recruitment TFIIH UVSSA repair. Conformational changes in lead ubiquitylation release before may continue repaired DNA.