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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Requirement for PBAF in Transcriptional Repression and Repair at DNA Breaks in Actively Transcribed Regions of Chromatin
Molecular Cell, Volume 55, No. 5, Year 2014
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Description
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. © 2014 The Authors.
Authors & Co-Authors
Kakarougkas, Andreas
United Kingdom, Brighton
University of Sussex
Ismail, A. M.
United Kingdom, Brighton
University of Sussex
Löbrich, Markus
Germany, Darmstadt
Technische Universität Darmstadt
Jeggo, Penny A.
United Kingdom, Brighton
University of Sussex
Downs, Jessica A.
United Kingdom, Brighton
University of Sussex
Statistics
Citations: 209
Authors: 5
Affiliations: 2
Identifiers
Doi:
10.1016/j.molcel.2014.06.028
ISSN:
10972765
Research Areas
Cancer
Genetics And Genomics