Cdc7p-Dbf4p regulates mitotic exit by inhibiting Polo kinase.

Cdc7p-Dbf4p regulates mitotic exit by inhibiting Polo kinase.

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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 Bicycle Trainers 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, Cuticle Cdc7p-Dbf4p prevents inappropriate exit from mitosis by inhibiting Polo kinase and functions in the spindle position checkpoint.