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Genes 2016, 7(11), 94; doi:10.3390/genes7110094

Recovery from the DNA Replication Checkpoint

Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, MN 55455, USA
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Author to whom correspondence should be addressed.
Academic Editor: Eishi Noguchi
Received: 26 September 2016 / Revised: 20 October 2016 / Accepted: 23 October 2016 / Published: 28 October 2016
(This article belongs to the Special Issue DNA Replication Controls)
View Full-Text   |   Download PDF [459 KB, uploaded 28 October 2016]   |  

Abstract

Checkpoint recovery is integral to a successful checkpoint response. Checkpoint pathways monitor progress during cell division so that in the event of an error, the checkpoint is activated to block the cell cycle and activate repair pathways. Intrinsic to this process is that once repair has been achieved, the checkpoint signaling pathway is inactivated and cell cycle progression resumes. We use the term “checkpoint recovery” to describe the pathways responsible for the inactivation of checkpoint signaling and cell cycle re-entry after the initial stress has been alleviated. The DNA replication or S-phase checkpoint monitors the integrity of DNA synthesis. When replication stress is encountered, replication forks are stalled, and the checkpoint signaling pathway is activated. Central to recovery from the S-phase checkpoint is the restart of stalled replication forks. If checkpoint recovery fails, stalled forks may become unstable and lead to DNA breaks or unusual DNA structures that are difficult to resolve, causing genomic instability. Alternatively, if cell cycle resumption mechanisms become uncoupled from checkpoint inactivation, cells with under-replicated DNA might proceed through the cell cycle, also diminishing genomic stability. In this review, we discuss the molecular mechanisms that contribute to inactivation of the S-phase checkpoint signaling pathway and the restart of replication forks during recovery from replication stress. View Full-Text
Keywords: DNA replication; S-phase checkpoint; checkpoint recovery; fork restart DNA replication; S-phase checkpoint; checkpoint recovery; fork restart
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Chaudhury, I.; Koepp, D.M. Recovery from the DNA Replication Checkpoint. Genes 2016, 7, 94.

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