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S-phase-specific activation of Cds1 kinase defines a subpathway of the checpoint response in Schizosaccharomyces pombe
journal contribution
posted on 2023-06-07, 20:50 authored by Howard D Lindsay, Dominic J Griffiths, Rhian J Edwards, Per U Christensen, Jo Murray, Fekret Osman, Nancy Walworth, Antony CarrAntony CarrCheckpoints that respond to DNA structure changes were originally defined by the inability of yeast mutants to prevent mitosis following DNA damage or S-phase arrest. Genetic analysis has subsequently identified subpathways of the DNA structure checkpoints, including the reversible arrest of DNA synthesis. Here, we show that the Cds1 kinase is required to slow S phase in the presence of DNA-damaging agents. Cds1 is phosphorylated and activated by S-phase arrest and activated by DNA damage during S phase, but not during G1 or G2. Activation of Cds1 during S phase is dependent on all six checkpoint Rad proteins, and Cds1 interacts both genetically and physically with Rad26. Unlike its Saccharomyces cerevisiae counterpart Rad53, Cds1 is not required for the mitotic arrest checkpoints and, thus, defines an S-phase specific subpathway of the checkpoint response. We propose a model for the DNA structure checkpoints that offers a new perspective on the function of the DNA structure checkpoint proteins. This model suggests that an intrinsic mechanism linking S phase and mitosis may function independently of the known checkpoint proteins.
History
Publication status
- Published
Journal
Genes & DevelopmentISSN
0890-9369Publisher
Cold Spring Harbor Laboratory PressPublisher URL
Issue
3Volume
12Page range
382-395ISBN
0890-9369Department affiliated with
- Sussex Centre for Genome Damage Stability Publications
Full text available
- No
Peer reviewed?
- Yes
Legacy Posted Date
2012-02-06Usage metrics
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