Cycling without the cyclosome: modeling a yeast strain lacking the APC

Area of Science:

• * Molecular and Cellular Biology
• * Yeast Genetics
• * Mathematical Modeling

Background:

• * The anaphase promoting complex (APC) is essential for cell cycle progression in Saccharomyces cerevisiae.
• * Previously, lethal APC gene deletions were suppressed by specific gene deletions (PDS1, CLB5) and SIC1 gene amplification.
• * This genetic manipulation aimed to induce oscillations in cyclin-dependent kinase (CDK) activity via cyclic Sic1 expression and degradation.

Purpose of the Study:

• * To model Saccharomyces cerevisiae strains lacking the anaphase promoting complex (APC).
• * To validate a mathematical model of the yeast cell cycle against experimental data from APC-deficient and other mutant strains.

Main Methods:

• * Utilized an updated mathematical model of the yeast cell cycle.
• * Simulated strains with deletions in APC genes, incorporating modifications to account for experimental observations.

Main Results:

• * The modified mathematical model accurately simulated the viability of APC-deficient (Apc-) strains.
• * The model successfully predicted the phenotypes of 27 other previously characterized yeast strains.
• * Minor discrepancies between model predictions and experimental results were identified.

Conclusions:

• * Mathematical modeling provides a powerful tool for understanding complex genetic perturbations in the yeast cell cycle.
• * The model's accuracy in simulating APC-deficient strains supports the proposed mechanism of cell cycle control through Sic1 oscillations.
• * Identified inconsistencies offer insights for refining the model and future research directions in yeast cell cycle regulation.