NDLI: Carboxy-terminal phosphorylation sites in Cdc25 contribute to enforcement of the DNA damage and replication checkpoints in fission yeast

Content Provider	Springer Nature Link
Author	Frazer, Corey Young, Paul G.
Copyright Year	2012
Abstract	In fission yeast and vertebrate cells, Cdc25 phosphatase is the target of checkpoint-mediated response to DNA replication blocks, DNA damage, and extracellular stress. As such, it is a key regulator of cell cycle progress and genomic stability. In fission yeast, phosphorylation of Cdc25 by the checkpoint kinases Cds1 and Chk1 and also Srk1 during stress creates a binding site for the 14-3-3 homolog Rad24; the complex is then exported from the nucleus. Cdc25 contains 12 potential serine/threonine phosphorylation sites that are phosphorylated in vitro by Cds1; 9 reside in the amino terminal half of the protein with the remaining sites are located in the extreme C-terminus. We have previously shown that deletion of the nine amino terminal sites results in degradation of the mutant protein while the checkpoint is enforced by the Mik1 kinase acting on Cdc2 tyrosine-15. Here, we examine the influence of the three C-terminal sites on the negative regulation of Cdc25. These sites are conserved in vertebrates and have been shown to be phosphorylated following DNA damage and replication blocks. We show that these three sites have a role in the negative regulation of Cdc25 following replication arrest, but perhaps more importantly they appear to particularly contribute to regulating the duration, and thus the effectiveness of the arrested state.
Starting Page	217
Ending Page	234
Page Count	18
File Format	PDF
ISSN	01728083
Journal	Current Genetics
Volume Number	58
Issue Number	4
e-ISSN	14320983
Language	English
Publisher	Springer-Verlag
Publisher Date	2012-07-18
Publisher Place	Berlin, Heidelberg
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Fission yeast Replication checkpoint Cdc25 Phosphorylation Chk1 Cds1 Cell Biology Proteomics Microbial Genetics and Genomics Biochemistry Microbiology Plant Sciences
Content Type	Text
Resource Type	Article
Subject	Genetics Medicine

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