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Requirement for PBAF in Transcriptional Repression and Repair at DNA Breaks in Actively Transcribed Regions of Chromatin

Kakarougkas, Andreas ; Ismail, Amani ; Chambers, Anna L. ; Riballo, Enriqueta ; Herbert, Alex D. ; Künzel, Julia ; Löbrich, Markus ; Jeggo, Penny A. ; Downs, Jessica A. (2021)
Requirement for PBAF in Transcriptional Repression and Repair at DNA Breaks in Actively Transcribed Regions of Chromatin.
In: Molecular Cell, 55 (5)
doi: 10.26083/tuprints-00018938
Article, Secondary publication, Publisher's Version

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Item Type: Article
Type of entry: Secondary publication
Title: Requirement for PBAF in Transcriptional Repression and Repair at DNA Breaks in Actively Transcribed Regions of Chromatin
Language: English
Date: 2021
Place of Publication: Darmstadt
Publisher: Elsevier
Journal or Publication Title: Molecular Cell
Volume of the journal: 55
Issue Number: 5
DOI: 10.26083/tuprints-00018938
Corresponding Links:
Origin: Secondary publication service
Abstract:

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.

Status: Publisher's Version
URN: urn:nbn:de:tuda-tuprints-189384
Classification DDC: 500 Science and mathematics > 570 Life sciences, biology
Divisions: 10 Department of Biology > Radiation Biology and DNA Repair
Date Deposited: 06 Sep 2021 12:30
Last Modified: 04 Aug 2023 07:27
URI: https://tuprints.ulb.tu-darmstadt.de/id/eprint/18938
PPN: 510321720
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