Mathematical model of the morphogenesis checkpoint in budding yeast

Area of Science:

• Cell Biology
• Molecular Biology
• Biophysics

Background:

• The morphogenesis checkpoint in budding yeast prevents cell cycle progression when bud formation is inhibited.
• Swe1 kinase is a key regulator, becoming active to halt the cell cycle in G2 phase.

Purpose of the Study:

• To propose and analyze a molecular network controlling Swe1 kinase activity.
• To integrate this network with cyclin-dependent kinase regulation for a comprehensive model.

Main Methods:

• Developing a molecular network model for Swe1 control based on published data from budding and fission yeast.
• Merging the Swe1 network with a cyclin-dependent kinase regulation model.
• Converting the integrated model into differential equations for numerical simulation.

Main Results:

• Simulations accurately reproduced phenotypes of numerous checkpoint mutants.
• The model predicts a novel indirect role for Hsl1 kinase in potent Swe1 inhibition, beyond its known role in degradation.
• The study supports the concept that cell size thresholds for cell cycle progression are elevated by checkpoints.

Conclusions:

• The proposed molecular network provides a robust framework for understanding Swe1 regulation within the morphogenesis checkpoint.
• Hsl1 kinase plays a dual role in controlling Swe1 activity, contributing to both degradation and potent inhibition.
• Morphogenesis checkpoint activation effectively increases the cell size requirement for cell cycle advancement.