Journal
EMBO JOURNAL
Volume 29, Issue 21, Pages 3723-3732Publisher
WILEY
DOI: 10.1038/emboj.2010.238
Keywords
53BP1; DNA damage; G1 checkpoint; ionizing radiation; TopBP1
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Funding
- Swiss National Foundation
- NIH
- European Commission
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TopBP1 is a checkpoint protein that colocalizes with ATR at sites of DNA replication stress. In this study, we show that TopBP1 also colocalizes with 53BP1 at sites of DNA double-strand breaks (DSBs), but only in the G1-phase of the cell cycle. Recruitment of TopBP1 to sites of DNA replication stress was dependent on BRCT domains 1-2 and 7-8, whereas recruitment to sites of DNA DSBs was dependent on BRCT domains 1-2 and 4-5. The BRCT domains 4-5 interacted with 53BP1 and recruitment of TopBP1 to sites of DNA DSBs in G1 was dependent on 53BP1. As TopBP1 contains a domain important for ATR activation, we examined whether it contributes to the G1 cell cycle checkpoint. By monitoring the entry of irradiated G1 cells into S-phase, we observed a checkpoint defect after siRNA-mediated depletion of TopBP1, 53BP1 or ATM. Thus, TopBP1 may mediate the checkpoint function of 53BP1 in G1. The EMBO Journal (2010) 29, 3723-3732. doi:10.1038/emboj.2010.238; Published online 24 September 2010
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