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BAF180 promotes cohesion and prevents genome instability and aneuploidy
journal contribution
posted on 2023-06-08, 17:39 authored by Peter M Brownlee, Anna L Chambers, Ross Cloney, Alessandro BianchiAlessandro Bianchi, Jessica A DownsBAF180, 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.
Funding
Analysis of regulation telomerase action and telomere capping function by the telomeric complex.; G0701428; MRC
History
Publication status
- Published
File Version
- Published version
Journal
Cell ReportsISSN
2211-1247Publisher
ElsevierExternal DOI
Issue
6Volume
6Page range
973-981Department affiliated with
- Sussex Centre for Genome Damage Stability Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2014-06-25First Open Access (FOA) Date
2014-06-25First Compliant Deposit (FCD) Date
2014-06-24Usage metrics
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