A Stochastic Model Correctly Predicts Changes in Budding Yeast Cell Cycle Dynamics upon Periodic Expression of <i>CLN2</i>

<div><p>In this study, we focus on a recent stochastic budding yeast cell cycle model. First, we estimate the model parameters using extensive data sets: phenotypes of 110 genetic strains, single cell statistics of wild type and <i>cln3</i> strains. Optimization of stochastic model parameters is achieved by an automated algorithm we recently used for a deterministic cell cycle model. Next, in order to test the predictive ability of the stochastic model, we focus on a recent experimental study in which forced periodic expression of <i>CLN2</i> cyclin (driven by <i>MET3</i> promoter in <i>cln3</i> background) has been used to synchronize budding yeast cell colonies. We demonstrate that the model correctly predicts the experimentally observed synchronization levels and cell cycle statistics of mother and daughter cells under various experimental conditions (numerical data that is not enforced in parameter optimization), in addition to correctly predicting the qualitative changes in size control due to forced <i>CLN2</i> expression. Our model also generates a novel prediction: under frequent <i>CLN2</i> expression pulses, G1 phase duration is bimodal among small-born cells. These cells originate from daughters with extended budded periods due to size control during the budded period. This novel prediction and the experimental trends captured by the model illustrate the interplay between cell cycle dynamics, synchronization of cell colonies, and size control in budding yeast.</p>