Identification of novel regulators of mitotic exit in Saccharomyces cerevisiae

Abstract

The division of a eukaryotic cell into two daughter cells is controlled by cyclin dependent kinase (CDK). Entry into mitosis is promoted by the activity of CDK complexed with mitotic cyclins. Upon faithful segregation of a full complement of DNA between each daughter cell, exit from mitosis proceeds. In order for cells to exit from mitosis and enter into G 1, mitotic CDKs must be inactivated. In Saccharomyces cerevisiae, mitotic exit is regulated by two signaling networks, the mitotic exit network (MEN) and the Cdc14 early anaphase release (FEAR) network. In this budding yeast, coordination of nuclear migration and mitotic exit is critical to prevent aneuploidy. A surveillance mechanism known as the spindle position checkpoint ensures that exit from mitosis only occurs when the anaphase nucleus is positioned along the mother - bud axis. The work presented here describes two screens that have isolated novel regulators of mitotic exit. A model for the regulation of mitotic exit by the gene KIN4 is proposed. This work identifies the protein kinase Kin4 as a component of the spindle position checkpoint.