BAF180 promotes cohesion and prevents genome instability and aneuploidy.
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Date
2014-03-27ICR Author
Author
Brownlee, PM
Chambers, AL
Cloney, R
Bianchi, A
Downs, JA
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Subject
Animals
Humans
Mice
Aneuploidy
Genomic Instability
HMGB Proteins
Nuclear Proteins
Transcription Factors
Gene Expression Regulation
Research team
Epigenetics and Genome Stability
Language
eng
Date accepted
2014-02-10
License start date
2014-03-06
Citation
Cell reports, 2014, 6 (6), pp. 973 - 981
Publisher
CELL PRESS