Abstract:
:Complete replication of the genome is an essential prerequisite for normal cell division, but a variety of factors can block the replisome, triggering replication stress and potentially causing mutation or cell death. The cellular response to replication stress involves recruitment of proteins to stabilize the replication fork and transmit a stress signal to pause the cell cycle and allow fork restart. We find that the ubiquitously expressed DNA damage response factor 53BP1 is required for the normal response to replication stress. Using primary, ex vivo B cells, we showed that a population of 53BP1-/- cells in early S phase is hypersensitive to short-term exposure to three different agents that induce replication stress. 53BP1 localizes to a subset of replication forks following induced replication stress, and an absence of 53BP1 leads to defective ATR-Chk1-p53 signaling and caspase 3-mediated cell death. Nascent replicated DNA additionally undergoes degradation in 53BP1-/- cells. These results show that 53BP1 plays an important role in protecting replication forks during the cellular response to replication stress, in addition to the previously characterized role of 53BP1 in DNA double-strand break repair.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Her J,Ray C,Altshuler J,Zheng H,Bunting SFdoi
10.1128/MCB.00472-17subject
Has Abstractpub_date
2018-03-29 00:00:00issue
8eissn
0270-7306issn
1098-5549pii
MCB.00472-17journal_volume
38pub_type
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