Regulation of the RNAPII Pool Is Integral to the DNA Damage Response.
Cell
; 180(6): 1245-1261.e21, 2020 03 19.
Article
en En
| MEDLINE
| ID: mdl-32142654
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 K1268), is the focal point for DNA-damage-response coordination. K1268 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.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Daño del ADN
/
ARN Polimerasa II
Límite:
Humans
Idioma:
En
Año:
2020
Tipo del documento:
Article