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Budding yeast Bub2 is localized at spindle pole bodies and activates the mitotic checkpoint via a different pathway from Mad2
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Pds1 and Esp1 control both anaphase and mitotic exit in normal cells and after DNA damage
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Through analysis of the DNA damage response, Pds1 is identified as an inhibitor of mitotic exit. Stabilized versions of Pds1 inhibit Clb2 degradation and prevent release from a cdc15 block. Clb2 degradation is delayed in esp1-1 mutants and sustained overexpression of ESP1 leads to Clb2 degradation in cells arrested by nocodazole or DNA damage, suggesting Pds1 might block mitotic exit by inhibiting Esp1.
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Tinker-Kulberg R.L., Morgan D.O. Pds1 and Esp1 control both anaphase and mitotic exit in normal cells and after DNA damage. Genes Dev. 13:1999;1936-1949. Through analysis of the DNA damage response, Pds1 is identified as an inhibitor of mitotic exit. Stabilized versions of Pds1 inhibit Clb2 degradation and prevent release from a cdc15 block. Clb2 degradation is delayed in esp1-1 mutants and sustained overexpression of ESP1 leads to Clb2 degradation in cells arrested by nocodazole or DNA damage, suggesting Pds1 might block mitotic exit by inhibiting Esp1.
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Pds1 of budding yeast has dual roles: Inhibition of anaphase initiation and regulation of mitotic exit
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A stabilized version of Pds1 blocks Clb2 degradation and cytokinesis, and prevents Cdh1 dephosphorylation. Whereas Clb2 degradation is delayed in esp1 mutants it is abrogated altogether by expression of stabilized Pds1, suggesting that Pds1 blocks Clb2 degradation and cytokinesis by a mechanism independent of Esp1.
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Cohen-Fix O., Koshland D. Pds1 of budding yeast has dual roles: inhibition of anaphase initiation and regulation of mitotic exit. Genes Dev. 13:1999;1950-1959. A stabilized version of Pds1 blocks Clb2 degradation and cytokinesis, and prevents Cdh1 dephosphorylation. Whereas Clb2 degradation is delayed in esp1 mutants it is abrogated altogether by expression of stabilized Pds1, suggesting that Pds1 blocks Clb2 degradation and cytokinesis by a mechanism independent of Esp1.
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Control of the DNA damage checkpoint by Chk1 and Rad53 protein kinases through distinct mechanisms
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Pds1 is identified as a target of the Chk1 kinase, which enforces a metaphase delay in response to DNA damage in budding yeast. In contrast, in fission yeast and mammals, Chk1 arrests cells prior to mitosis via control of inhibitory tyrosine phosphorylation on mitotic CDK complexes. Rad53 appears to act in a parallel branch of the DNA-damage checkpoint response, possibly by inhibiting the polo-like kinase Cdc5 and thereby delaying both anaphase onset and mitotic exit. The latter observation is consistent with the observed role of Cdc5 in recovery from the DNA damage imposed cell cycle arrest.
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Sanchez Y., Bachant J., Wang H., Hu F., Liu D., Tetzlaff M., Elledge S.J. Control of the DNA damage checkpoint by Chk1 and Rad53 protein kinases through distinct mechanisms. Science. 286:1999;1166-1171. Pds1 is identified as a target of the Chk1 kinase, which enforces a metaphase delay in response to DNA damage in budding yeast. In contrast, in fission yeast and mammals, Chk1 arrests cells prior to mitosis via control of inhibitory tyrosine phosphorylation on mitotic CDK complexes. Rad53 appears to act in a parallel branch of the DNA-damage checkpoint response, possibly by inhibiting the polo-like kinase Cdc5 and thereby delaying both anaphase onset and mitotic exit. The latter observation is consistent with the observed role of Cdc5 in recovery from the DNA damage imposed cell cycle arrest.
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A late mitotic regulatory network controlling cyclin destruction in Saccharomyces cerevisiae
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Destruction of the CDC28/CLB mitotic kinase is not required for the metaphase to anaphase transition in budding yeast
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Cdc20 is essential for the cyclosome-mediated proteolysis of both Pds1 and Clb2 during M phase in budding yeast
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Lim H.H., Goh P.Y., Surana U. Cdc20 is essential for the cyclosome-mediated proteolysis of both Pds1 and Clb2 during M phase in budding yeast. Curr Biol. 8:1998;231-234.
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Deregulated cyclin E induces chromosome instability
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Inappropriate cyclin E activity, either through overexpression of wild-type cyclin E or stabilized forms of cyclin E, causes genome instability in immortalized rat embryo fibroblasts and human breast epithelial cells. Excess cyclin E interferes predominantly with DNA replication, perhaps by preventing formation of pre-replicative origins of DNA replication.
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Spruck C.H., Won K.A., Reed S.I. Deregulated cyclin E induces chromosome instability. Nature. 401:1999;297-300. Inappropriate cyclin E activity, either through overexpression of wild-type cyclin E or stabilized forms of cyclin E, causes genome instability in immortalized rat embryo fibroblasts and human breast epithelial cells. Excess cyclin E interferes predominantly with DNA replication, perhaps by preventing formation of pre-replicative origins of DNA replication.
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Spruck, C.H.1
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