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Requirement for PBAF in transcriptional repression and repair at DNA breaks in actively transcribed regions of chromatin

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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 Downs
Actively 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 Cell

ISSN

1097-2765

Publisher

Elsevier (Cell Press)

Issue

5

Volume

55

Page range

723-732

Department affiliated with

  • Sussex Centre for Genome Damage Stability Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2014-07-29

First Open Access (FOA) Date

2014-07-29

First Compliant Deposit (FCD) Date

2014-07-28

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