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A CSB-PAF1C axis restores processive transcription elongation after DNA damage repair
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A CSB-PAF1C axis restores processive transcription elongation after DNA damage repair
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Journal Article
A CSB-PAF1C axis restores processive transcription elongation after DNA damage repair
2021
Overview
Bulky DNA lesions in transcribed strands block RNA polymerase II (RNAPII) elongation and induce a genome-wide transcriptional arrest. The transcription-coupled repair (TCR) pathway efficiently removes transcription-blocking DNA lesions, but how transcription is restored in the genome following DNA repair remains unresolved. Here, we find that the TCR-specific CSB protein loads the PAF1 complex (PAF1C) onto RNAPII in promoter-proximal regions in response to DNA damage. Although dispensable for TCR-mediated repair, PAF1C is essential for transcription recovery after UV irradiation. We find that PAF1C promotes RNAPII pause release in promoter-proximal regions and subsequently acts as a processivity factor that stimulates transcription elongation throughout genes. Our findings expose the molecular basis for a non-canonical PAF1C-dependent pathway that restores transcription throughout the human genome after genotoxic stress.
The transcription-coupled repair pathway removes transcription-blocking DNA lesions, but how transcription is restored following DNA repair is not clear. Here the authors reveal that the PAF1 complex, while dispensable for the repair process, restores transcription after DNA damage.
Publisher
Nature Publishing Group UK,Nature Portfolio
Subject
/ 82/58
/ DNA Repair Enzymes - metabolism
/ Humanities and Social Sciences
/ Humans
/ Poly-ADP-Ribose Binding Proteins - genetics
/ Poly-ADP-Ribose Binding Proteins - metabolism
/ RNA Polymerase II - genetics
/ RNA Polymerase II - metabolism
/ Science
/ Transcription Factors - genetics
