Cdc7p-Dbf4p Regulates Mitotic Exit by Inhibiting Polo Kinase |
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Authors: | Charles T Miller Carrie Gabrielse Ying-Chou Chen and Michael Weinreich |
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Institution: | 1.Graduate Program in Cell and Molecular Biology, Michigan State University, East Lansing, Michigan, United States of America;2.Laboratory of Chromosome Replication, Van Andel Research Institute, Grand Rapids, Michigan, United States of America;3.Graduate Program in Genetics, Michigan State University, East Lansing, Michigan, United States of America;National Institute of Diabetes and Digestive and Kidney Diseases, United States of America |
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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. |
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