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Regulation of the RNAPII Pool Is Integral to the DNA Damage Response.
- Source :
-
Cell [Cell] 2020 Mar 19; Vol. 180 (6), pp. 1245-1261.e21. Date of Electronic Publication: 2020 Mar 05. - Publication Year :
- 2020
-
Abstract
- In response to transcription-blocking DNA damage, cells orchestrate a multi-pronged reaction, involving transcription-coupled DNA repair, degradation of RNA polymerase II (RNAPII), and genome-wide transcription shutdown. Here, we provide insight into how these responses are connected by the finding that ubiquitylation of RNAPII itself, at a single lysine (RPB1 K <subscript>1268</subscript> ), is the focal point for DNA-damage-response coordination. K <subscript>1268</subscript> ubiquitylation affects DNA repair and signals RNAPII degradation, essential for surviving genotoxic insult. RNAPII degradation results in a shutdown of transcriptional initiation, in the absence of which cells display dramatic transcriptome alterations. Additionally, regulation of RNAPII stability is central to transcription recovery-persistent RNAPII depletion underlies the failure of this process in Cockayne syndrome B cells. These data expose regulation of global RNAPII levels as integral to the cellular DNA-damage response and open the intriguing possibility that RNAPII pool size generally affects cell-specific transcription programs in genome instability disorders and even normal cells.<br />Competing Interests: Declaration of Interests The authors declare no competing interests.<br /> (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)
Details
- Language :
- English
- ISSN :
- 1097-4172
- Volume :
- 180
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Cell
- Publication Type :
- Academic Journal
- Accession number :
- 32142654
- Full Text :
- https://doi.org/10.1016/j.cell.2020.02.009