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

Andreas Kakarougkas, Amani Ismail, Anna L Chambers, Enriqueta Riballo, Alex D Herbert, Julia Künzel, Markus Löbrich, Penny A Jeggo, Jessica A Downs

Research output: Contribution to journalArticle (Academic Journal)peer-review

148 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)723-732
Number of pages10
JournalMolecular Cell
Volume55
Issue number5
DOIs
Publication statusPublished - 4 Sep 2014

Bibliographical note

Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Keywords

  • Binding Sites
  • Cell Line, Tumor
  • Chromosomal Proteins, Non-Histone
  • DNA Breaks
  • DNA End-Joining Repair
  • DNA Repair
  • Gene Expression Regulation
  • HeLa Cells
  • Histones
  • Humans
  • Nuclear Proteins
  • Phosphorylation
  • Transcription Factors
  • Ubiquitination

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