Distinct phosphatases mediate the deactivation of the DNA damage checkpoint kinase rad53.

Distinct phosphatases mediate the deactivation of the DNA damage checkpoint kinase rad53. Research Abstract Details 

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Distinct phosphatases mediate the deactivation of the DNA damage checkpoint kinase rad53. Abstract Text:

The DNA damage checkpoint regulates DNA replication and arrests cell cycle progression in response to genotoxic stress. In Saccharomyces cerevisiae, the protein kinase Rad53 plays a central role in preventing genomic instability and maintaining viability in the presence of replication stress and DNA damage. Activation of Rad53 depends on phosphorylation by the upstream kinase Mec1, followed by autophosphorylation on multiple residues. Also critical for cell viability, the molecular mechanism of Rad53 deactivation remains incompletely understood. Rad53 dephosphorylation after repair of a persistent double strand break in G(2)/M has been shown to depend on the presence of the PP2C-type phosphatases Ptc2 and Ptc3. More recently, the PP2A-like protein phosphatase Pph3 has been shown to be required to dephosphorylate Rad53 after DNA methylation damage in S phase. However, we show here that Ptc2/3 are dispensable for Rad53 deactivation after replication stress or DNA methylation damage. Pph3 is also dispensable for the deactivation of Rad53 after replication stress. In addition, Rad53 kinase activity is still deactivated in pph3 null cells after DNA methylation damage, despite persistent Rad53 hyperphosphorylation. Finally, a strain in which the three phosphatases are deleted shows a severe defect in Rad53 kinase deactivation after DNA methylation damage but not after replication stress. In all, our results suggest that distinct phosphatases operate to return Rad53 to its basal state after different genotoxic stresses and that a yet unidentified phosphatase may be responsible for the deactivation of Rad53 after replication stress.

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Distinct phosphatases mediate the deactivation of the DNA damage checkpoint kinase rad53. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: The Journal of biological chemistry

VOLUME: 283

Page Numbers: 17123-30

Journal Abbreviation: J. Biol. Chem.

ISSN: 0021-9258

DAY: 25

MONTH: 04

YEAR: 2008

Distinct phosphatases mediate the deactivation of the DNA damage checkpoint kinase rad53. Information

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LANGUAGE: eng

NlmUniqueID: 2985121

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Grant and Affiliation Information for Distinct phosphatases mediate the deactivation of the DNA damage checkpoint kinase rad53.

AFFILIATION: Department of Biochemistry and Molecular Biology, School of Medicine.

Country: United States

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MEDLINETA: J Biol Chem

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