Journal
JOURNAL OF CELL BIOLOGY
Volume 191, Issue 1, Pages 45-60Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.201003034
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Funding
- Canadian Institute of Health Research (CIHR) [MOP15334]
- Alberta Cancer Board (ACB)
- Cell Imaging Facility at the Cross Cancer Institute
- AIHS
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Polycomb group (PcG) proteins are major determinants of cell identity, stem cell pluripotency, and epigenetic gene silencing during development. The polycomb repressive complex 1, which contains BMI1, RING1, and RING2, functions as an E3-ubuiquitin ligase. We found that BMI1 and RING2 are recruited to sites of DNA double-strand breaks (DSBs) where they contribute to the ubiquitylation of gamma-H2AX. In the absence of BMI1, several proteins dependent on ubiquitin signaling, including 53BP1, BRCA1, and RAP80, are impaired in recruitment to DSBs. Loss of BMI1 sensitizes cells to ionizing radiation to the same extent as loss of RNF8. The simultaneous depletion of both proteins revealed an additive increase in radiation sensitivity. These data uncover an unexpected link between the polycomb and the DNA damage response pathways, and suggest a novel function for BMI1 in maintaining genomic stability.
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