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PLoS Genet. 2009 May;5(5):e1000498. doi: 10.1371/journal.pgen.1000498. Epub 2009 May 29.

Cdc7p-Dbf4p regulates mitotic exit by inhibiting Polo kinase.

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  • 1Graduate Program in Cell and Molecular Biology, Michigan State University, East Lansing, MI, USA.

Abstract

Cdc7p-Dbf4p is a conserved protein kinase required for the initiation of DNA replication. The Dbf4p regulatory subunit binds Cdc7p and is essential for Cdc7p kinase activation, however, the N-terminal third of Dbf4p is dispensable for its essential replication activities. Here, we define a short N-terminal Dbf4p region that targets Cdc7p-Dbf4p kinase to Cdc5p, the single Polo kinase in budding yeast that regulates mitotic progression and cytokinesis. Dbf4p mediates an interaction with the Polo substrate-binding domain to inhibit its essential role during mitosis. Although Dbf4p does not inhibit Polo kinase activity, it nonetheless inhibits Polo-mediated activation of the mitotic exit network (MEN), presumably by altering Polo substrate targeting. In addition, although dbf4 mutants defective for interaction with Polo transit S-phase normally, they aberrantly segregate chromosomes following nuclear misorientation. Therefore, Cdc7p-Dbf4p prevents inappropriate exit from mitosis by inhibiting Polo kinase and functions in the spindle position checkpoint.

PMID:
19478884
[PubMed - indexed for MEDLINE]
PMCID:
PMC2682205
Free PMC Article
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