Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 107, Issue 32, Pages 14280-14285Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1009559107
Keywords
cancer; PBAF; SWI/SNF; p21
Categories
Funding
- National Institutes of Health and Department of Defense
- Pathology Department at the Massachusetts General Hospital [T32CA09216]
- Burroughs Wellcome Fund
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A variety of tumor-suppressor mechanisms exist to promote genome integrity and organismal survival. One such mechanism is cellular senescence. In response to replicative aging, DNA damage, and oncogenic stimuli, the p53 and Rb pathways are activated to prevent the proliferation of damaged cells by inducing senescence or apoptosis. We have performed a loss-of-function genetic screen in primary human cells to identify components of the senescence machinery. Here we describe BRD7 and BAF180 as unique regulators of replicative senescence in human cells. Both regulate p53 transcriptional activity toward a subset of its target genes required for replicative and oncogenic stress senescence induction, and BRD7 physically interacts with p53. BRD7 is a deletion target in human cancer, suggesting that loss of BRD7 may provide an additional mechanism to antagonize p53 function in cancer cells.
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