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Cdc7p-Dbf4p regulates mitotic exit by inhibiting Polo kinase.

PLoS genetics | May 29, 2009

http://www.ncbi.nlm.nih.gov/pubmed/19478884

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.

Pubmed ID: 19478884 RIS Download

Mesh terms: Cell Cycle | Cell Cycle Proteins | Gene Expression Regulation, Fungal | Mitosis | Protein Binding | Protein Kinases | Protein Structure, Tertiary | Protein-Serine-Threonine Kinases | Saccharomyces cerevisiae | Saccharomyces cerevisiae Proteins

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