Regulation of the RNAPII Pool Is Integral to the DNA Damage Response
Ana Tufegdžić Vidaković, Richard Mitter, Gavin Kelly, Michelle Neumann, Michelle T. Harreman, Marta Rodríguez‐Martínez, Anna E. Herlihy, Juston C. Weems, Stefan Boeing, Vesela Encheva, Liam Gaul, Laura Milligan, David Tollervey, Ronald Conaway, Joan Conaway, Ambrosius P. Snijders, Aengus Stewart, Jesper Q. Svejstrup
Abstract
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.