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

Kakarougkas, Andreas, Ismail, Amani, Chambers, Anna, Riballo, Queti, Herbert, Alex, Kunzel, Julia, Lobrich, Markus, Jeggo, Penny and Downs, Jessica (2014) Requirement for PBAF in transcriptional repression and repair at DNA breaks in actively transcribed regions of chromatin. Molecular Cell, 55 (5). pp. 723-732. ISSN 1097-2765

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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.

Item Type: Article
Schools and Departments: School of Life Sciences > Sussex Centre for Genome Damage and Stability
Subjects: Q Science > QH Natural history > QH0301 Biology > QH0426 Genetics
Depositing User: Jill Kirby
Date Deposited: 29 Jul 2014 08:22
Last Modified: 06 Mar 2017 17:42
URI: http://sro.sussex.ac.uk/id/eprint/49422

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