UMass Chan Affiliations
Graduate School of Biomedical Sciences, Interdisciplinary Graduate ProgramDepartment of Biochemistry and Molecular Pharmacology
Document Type
Journal ArticlePublication Date
2017-02-17Keywords
ATRChk1
DNA damage
fork stability
intra-S checkpoint
origin regulation
Biochemistry
Cell Biology
Genetics
Molecular Biology
Metadata
Show full item recordAbstract
Faithful duplication of the genome is a challenge because DNA is susceptible to damage by a number of intrinsic and extrinsic genotoxins, such as free radicals and UV light. Cells activate the intra-S checkpoint in response to damage during S phase to protect genomic integrity and ensure replication fidelity. The checkpoint prevents genomic instability mainly by regulating origin firing, fork progression, and transcription of G1/S genes in response to DNA damage. Several studies hint that regulation of forks is perhaps the most critical function of the intra-S checkpoint. However, the exact role of the checkpoint at replication forks has remained elusive and controversial. Is the checkpoint required for fork stability, or fork restart, or to prevent fork reversal or fork collapse, or activate repair at replication forks? What are the factors that the checkpoint targets at stalled replication forks? In this review, we will discuss the various pathways activated by the intra-S checkpoint in response to damage to prevent genomic instability.Source
Genes (Basel). 2017 Feb 17;8(2). pii: E74. doi: 10.3390/genes8020074. Link to article on publisher's siteDOI
10.3390/genes8020074Permanent Link to this Item
http://hdl.handle.net/20.500.14038/40291PubMed ID
28218681Related Resources
Link to Article in PubMedRights
Copyright © 2017 by the authors.Distribution License
http://creativecommons.org/licenses/by/4.0/ae974a485f413a2113503eed53cd6c53
10.3390/genes8020074