PIIS1097276514005371.pdf (2.03 MB)
Requirement for PBAF in transcriptional repression and repair at DNA breaks in actively transcribed regions of chromatin
journal contribution
posted on 2023-06-08, 17:57 authored by Andreas Kakarougkas, Amani Ismail, Anna Chambers, Queti Riballo, Alex Herbert, Julia Kunzel, Markus Lobrich, Penny Jeggo, Jessica DownsActively transcribed regions of the genome are vulnerable to genomic instability. Recently, it was discovered that transcription is repressed in response to neighboring DNA double-strand breaks (DSBs). It is not known whether a failure to silence transcription flanking DSBs has any impact on DNA repair efficiency or whether chromatin remodelers contribute to the process. Here, we show that the PBAF remodeling complex is important for DSB-induced transcriptional silencing and promotes repair of a subset of DNA DSBs at early time points, which can be rescued by inhibiting transcription globally. An ATM phosphorylation site on BAF180, a PBAF subunit, is required for both processes. Furthermore, we find that subunits of the PRC1 and PRC2 polycomb group complexes are similarly required for DSB-induced silencing and promoting repair. Cancer-associated BAF180 mutants are unable to restore these functions, suggesting PBAF's role in repressing transcription near DSBs may contribute to its tumor suppressor activity.
Funding
MR/K001604/1; MRC
History
Publication status
- Published
File Version
- Published version
Journal
Molecular CellISSN
1097-2765Publisher
Elsevier (Cell Press)External DOI
Issue
5Volume
55Page range
723-732Department affiliated with
- Sussex Centre for Genome Damage Stability Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2014-07-29First Open Access (FOA) Date
2014-07-29First Compliant Deposit (FCD) Date
2014-07-28Usage metrics
Categories
No categories selectedKeywords
Licence
Exports
RefWorks
BibTeX
Ref. manager
Endnote
DataCite
NLM
DC