Requirement for PBAF in transcriptional repression and repair at DNA breaks in actively transcribed regions of chromatin.
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Date
2014-09-04ICR Author
Author
Kakarougkas, A
Ismail, A
Chambers, AL
Riballo, E
Herbert, AD
Künzel, J
Löbrich, M
Jeggo, PA
Downs, JA
Type
Journal Article
Metadata
Show full item recordAbstract
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.
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Subject
Cell Line, Tumor
Hela Cells
Humans
Nuclear Proteins
Chromosomal Proteins, Non-Histone
Histones
Transcription Factors
DNA Repair
Gene Expression Regulation
Binding Sites
Phosphorylation
DNA Breaks
Ubiquitination
DNA End-Joining Repair
Research team
Epigenetics and Genome Stability
Language
eng
Date accepted
2014-06-19
License start date
2014-09
Citation
Molecular cell, 2014, 55 (5), pp. 723 - 732
Publisher
CELL PRESS