Cdk1 Modulation Ensures the Coordination of Cell-Cycle Events during the Switch from Meiotic Prophase to Mitosis

Abstract

Budding yeast cells that enter the developmental path of meiosis do not commit to finishing meiosis until after prophase I and the realization of such meiosis-specific events as pairing of homologous chromosomes and initiation of recombination. If the meiosis-inducing signal is withdrawn prior to commitment, cells exit meiosis and return to mitosis. The timing of this transition poses a singular problem for maintaining genome integrity. Cells in meiotic prophase have already replicated their DNA, but they have not undergone the morphological changes intrinsic to mitosis, including budding. Successful re-entry into mitosis requires that these cells bud but not rereplicate their DNA, reversing the normal order of mitosis. This study focuses on the cellular mechanisms that permit this dramatically altered order of cell-cycle events. By developing a microfluidics assay to monitor individual cells, we show that the successful transition from meiotic prophase to mitosis requires the modulation of Cdk1 activity to coordinate cell-cycle events. The S. cerevisiae Wee1 homolog Swe1 prevents the formation of multinucleate cells by restraining M phase CDK activity to allow bud formation prior to nuclear division. The remaining S phase CDK activity promotes bud formation and prevents origin licensing so that DNA cannot rereplicate between bud formation and nuclear division. Once a bud has formed, M phase CDK drives cells through a normal mitotic division. Our study uncovers the essential requirement of Swe1 to modulate CDK activity to coordinate cell-cycle events and maintain genome integrity during the transition from meiotic prophase to mitosis.