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

Area of Science:

• Cell Biology
• Molecular Biology
• Genetics

Background:

• Meiotic recombination defects trigger a checkpoint delaying meiotic prophase I exit in budding yeast.
• This arrest is reinforced by Swe1-mediated inhibitory phosphorylation of Cdk1/Cdc28.
• Meiosis I entry relies on removing inhibitory phosphorylation, regulated by Swe1 and Mih1 phosphatase.

Purpose of the Study:

• To elucidate the rewiring of the regulatory network at the prophase I-meiosis I transition.
• To define the roles of Swe1 and Cdc5 in checkpoint maintenance and cell cycle progression during meiosis.

Main Methods:

• Investigated checkpoint activation and maintenance using budding yeast models.
• Analyzed the roles of Swe1, Mih1, and Cdc5 in regulating Cdk1/Cdc28 phosphorylation and activity.
• Examined Swe1 degradation mechanisms and Mih1 nuclear translocation.

Main Results:

• Swe1 is essential for checkpoint maintenance but not its initial activation.
• Cdc5 promotes Cdk1 activation by inducing Swe1 degradation and facilitating Mih1 nuclear translocation.
• Unlike in mitosis, Cdc5-mediated Swe1 degradation does not require CDK priming and can occur via artificial colocalization.

Conclusions:

• Uncovered an additional role for Cdc5 in promoting meiotic cell cycle progression.
• Highlighted the adaptation of conserved cell cycle regulators for meiotic processes.
• Demonstrated how the Swe1/Mih1 regulatory network is rewired to facilitate the prophase I-meiosis I transition.