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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. (Publisher's Version)
In: Molecular Cell, 55 (5), pp. 723-732. Elsevier, ISSN 1097-2765,
DOI: 10.26083/tuprints-00018938,
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Item Type: Article
Origin: Secondary publication service
Status: Publisher's Version
Title: Requirement for PBAF in Transcriptional Repression and Repair at DNA Breaks in Actively Transcribed Regions of Chromatin
Language: English
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.

Journal or Publication Title: Molecular Cell
Journal volume: 55
Number: 5
Publisher: Elsevier
Classification DDC: 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie
Divisions: 10 Department of Biology > Radiation Biology and DNA Repair
Date Deposited: 06 Sep 2021 12:30
Last Modified: 06 Sep 2021 12:30
DOI: 10.26083/tuprints-00018938
Corresponding Links:
URN: urn:nbn:de:tuda-tuprints-189384
URI: https://tuprints.ulb.tu-darmstadt.de/id/eprint/18938
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