BAF180 promotes cohesion and prevents genome instability and aneuploidy

Brownlee, Peter M, Chambers, Anna L, Cloney, Ross, Bianchi, Alessandro and Downs, Jessica A (2014) BAF180 promotes cohesion and prevents genome instability and aneuploidy. Cell Reports, 6 (6). pp. 973-981. ISSN 2211-1247

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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.

Item Type: Article
Schools and Departments: School of Life Sciences > Sussex Centre for Genome Damage and Stability
Subjects: Q Science
Depositing User: Jill Kirby
Date Deposited: 25 Jun 2014 09:02
Last Modified: 07 Mar 2017 06:03
URI: http://sro.sussex.ac.uk/id/eprint/49053

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Project NameSussex Project NumberFunderFunder Ref
Analysis of regulation telomerase action andĀ telomereĀ capping function by the telomeric complex.G0701428MRCUnset