BAF180 promotes cohesion and prevents genome instability and aneuploidy.
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Embargo End Date
ICR Authors
Authors
Brownlee, PM
Chambers, AL
Cloney, R
Bianchi, A
Downs, JA
Chambers, AL
Cloney, R
Bianchi, A
Downs, JA
Document Type
Journal Article
Date
2014-03-27
Date Accepted
2014-02-10
Abstract
BAF180, a subunit of the PBAF chromatin remodeling complex, is frequently mutated in cancer. Although PBAF regulates transcription, it remains unclear whether this is what drives tumorigenesis in cells lacking BAF180. Based on data from yeast, we hypothesized that BAF180 may prevent tumorigenesis by promoting cohesion. Here, we show BAF180 is required for centromeric cohesion in mouse and human cells. Mutations identified in tumor samples are unable to support this activity, and also compromise cohesion-dependent functions in yeast. We provide evidence of genome instability in line with loss of cohesion, and importantly, we find dynamic chromosome instability following DNA damage in cells lacking BAF180. These data demonstrate a function for BAF180 in promoting genome stability that is distinct from its well-characterized role in transcriptional regulation, uncovering a potent mechanism for its tumor-suppressor activity.
Citation
Cell reports, 2014, 6 (6), pp. 973 - 981
Source Title
Publisher
CELL PRESS
ISSN
2211-1247
eISSN
2211-1247
Collections
Research Team
Epigenetics and Genome Stability