title: Stochastic exit from mitosis in budding yeast: model predictions and experimental observations.
abstract: Unlike many mutants that are completely viable or inviable, the CLB2-dbΔ clb5Δ mutant of Saccharomyces cerevisiae is inviable in glucose but partially viable on slower growth media such as raffinose. On raffinose, the mutant cells can bud and divide but in each cycle there is a chance that a cell will fail to divide (telophase arrest), causing it to exit the cell cycle. This effect gives rise to a stochastic phenotype that cannot be explained by a deterministic model. We measure the inter-bud times of wild type and mutant cells growing on raffinose and compute statistics and distributions to characterize the mutant's behavior. We convert a detailed deterministic model of the budding yeast cell cycle to a stochastic model and determine the extent to which it captures the stochastic phenotype of the mutant strain. Predictions of the mathematical model are in reasonable agreement with our experimental data and suggest directions for improving the model. Ultimately, the ability to accurately model stochastic phenotypes may prove critical to understanding disease and therapeutic interventions in higher eukaryotes.
authors.affiliation: Virginia Polytechnic Institute and State University, Blacksburg, VA, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Ball
authors.forename: Tae-Hyuk
authors.initials: TH
authors.lastname: Ahn
authors.forename: Pengyuan
authors.initials: P
authors.lastname: Wang
authors.forename: Katherine C
authors.initials: KC
authors.lastname: Chen
authors.forename: Yang
authors.initials: Y
authors.lastname: Cao
authors.forename: John J
authors.initials: JJ
authors.lastname: Tyson
authors.forename: Jean
authors.initials: J
authors.lastname: Peccoud
authors.forename: William T
authors.initials: WT
authors.lastname: Baumann
mesh_terms: D019926:Cyclin B / Q000235:genetics / Q000378:metabolism; D008938:Mitosis / Q000187:drug effects; D008954:Models, Biological; D010641:Phenotype; D011887:Raffinose / Q000494:pharmacology; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D013269:Stochastic Processes
chemical_list: C093749:CLB2 protein, S cerevisiae; C076558:CLB5 protein, S cerevisiae; D019926:Cyclin B; D029701:Saccharomyces cerevisiae Proteins; D011887:Raffinose