PLoS Genetics · 2009 · 47 citations · 64 references
Life SciencesCell BiologyMolecular BiologyCell CycleCell DivisionDna ReplicationCell Cycle ControlCell-cycle CheckpointsCell-cycle RegulationMitosisMitotic ExitS PhaseMitosis RegulationMitotic Checkpoint SignalingMitotic Exit CheckpointMitotic Exit NetworkMitotic Exit RegulationMitotic Kinase ActivationMitotic Progression ControlPolo-like Kinase Function
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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Genetic Control of the Cell Division Cycle in Yeast
Leland H. Hartwell, Joseph G. Culotti, John R. Pringle et al. · Science · 1974 · 1.6K citations