Stochastic exit from mitosis in budding yeast: model predictions and experimental observations

Area of Science:

• Cell Biology
• Mathematical Biology
• Genetics

Background:

• The CLB2-dbΔ clb5Δ mutant in Saccharomyces cerevisiae displays unique viability characteristics, being inviable in glucose but partially viable on raffinose.
• This partial viability is associated with a stochastic cell cycle phenotype, specifically telophase arrest and subsequent cell cycle exit, which deterministic models cannot fully explain.

Purpose of the Study:

• To characterize the stochastic cell division behavior of the CLB2-dbΔ clb5Δ mutant on raffinose.
• To develop and validate a stochastic mathematical model of the budding yeast cell cycle that can capture the observed mutant phenotype.

Main Methods:

• Experimental measurement of inter-bud times in wild type and CLB2-dbΔ clb5Δ mutant yeast cells.
• Statistical analysis and distribution computation to characterize cell cycle behavior.
• Conversion of a deterministic cell cycle model into a stochastic model for comparison with experimental data.

Main Results:

• The CLB2-dbΔ clb5Δ mutant exhibits a stochastic phenotype on raffinose, with cells occasionally failing to divide and exiting the cell cycle.
• The developed stochastic mathematical model demonstrated reasonable agreement with the experimental data.
• The model's predictions suggest potential avenues for further refinement and understanding of the mutant's behavior.

Conclusions:

• Stochastic modeling is crucial for accurately describing and understanding phenotypes like that of the CLB2-dbΔ clb5Δ mutant.
• The validated stochastic model provides insights into the yeast cell cycle and its perturbations.
• Accurate modeling of stochastic phenotypes is essential for advancing the understanding of diseases and therapeutic strategies in higher eukaryotes.