Polo-like kinase Cdc5 orchestrates Cdk1 regulation via Swe1 and Mih1 during meiotic prophase I exit

Defects in chromosome synapsis and meiotic recombination activate a checkpoint that, in budding yeast, delays exit from meiotic prophase I by inhibiting the Ndt80-dependent expression of regulators including the cyclin CLB1 and the polo-like kinase (PLK) CDC5. Additionally, Swe1-mediated inhibitory phosphorylation of cyclin-dependent kinase 1 (Cdk1/Cdc28) reinforces this arrest. Once the checkpoint is released, Cdk1 activation is essential for meiosis I entry and requires removal of inhibitory phosphorylation on tyrosine 19, governed by the opposing activities of the Swe1 kinase and the Mih1 phosphatase. Here, we dissect how this network is rewired at the prophase I to meiosis I transition. We show that Swe1 is essential for checkpoint maintenance, but not for its initial activation. We also demonstrate that Cdc5 promotes Cdk1 activation through a dual mechanism: by inducing Swe1 degradation and facilitating Mih1 nuclear translocation. Unlike in mitosis, Cdc5-dependent Swe1 degradation in meiosis does not require CDK-mediated priming and can occur when both proteins are artificially colocalized, indicating a distinct regulatory mode. Our findings uncover a novel function for Cdc5 in promoting meiotic cell cycle progression beyond its known roles in recombination and synaptonemal complex disassembly, highlighting how conserved cell cycle regulators are adapted to meiosis.