Surviving chromosome replication: the many roles of the S-phase checkpoint pathway.
Affiliation
Paterson Institute for Cancer Research, University of Manchester, Wilmslow Road, Manchester M20 4BX, UK. klabib@picr.man.ac.ukIssue Date
2011-12-27
Metadata
Show full item recordAbstract
Checkpoints were originally identified as signalling pathways that delay mitosis in response to DNA damage or defects in chromosome replication, allowing time for DNA repair to occur. The ATR (ataxia- and rad-related) and ATM (ataxia-mutated) protein kinases are recruited to defective replication forks or to sites of DNA damage, and are thought to initiate the DNA damage response in all eukaryotes. In addition to delaying cell cycle progression, however, the S-phase checkpoint pathway also controls chromosome replication and DNA repair pathways in a highly complex fashion, in order to preserve genome integrity. Much of our understanding of this regulation has come from studies of yeasts, in which the best-characterized targets are the stimulation of ribonucleotide reductase activity by multiple mechanisms, and the inhibition of new initiation events at later origins of DNA replication. In addition, however, the S-phase checkpoint also plays a more enigmatic and apparently critical role in preserving the functional integrity of defective replication forks, by mechanisms that are still understood poorly. This review considers some of the key experiments that have led to our current understanding of this highly complex pathway.Citation
Surviving chromosome replication: the many roles of the S-phase checkpoint pathway. 2011, 366 (1584):3554-61 Philos Trans R Soc Lond B Biol SciJournal
Philosophical Transactions of the Royal Society of London. Series B, Biological SciencesDOI
10.1098/rstb.2011.0071PubMed ID
22084382Type
ArticleLanguage
enISSN
1471-2970ae974a485f413a2113503eed53cd6c53
10.1098/rstb.2011.0071