Stochastic exit from mitosis in budding yeast: Model predictions and experimental observations |
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Authors: | David A Ball Tae-Hyuk Ahn Pengyuan Wang Katherine C Chen Yang Cao John J Tyson Jean Peccoud William T Baumann |
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Institution: | 1.Virginia Bioinformatics Institute; Blacksburg, VA USA;2.Department of Computer Science; Virginia Polytechnic Institute and State University; Blacksburg, VA USA;3.Department of Biological Sciences; Virginia Polytechnic Institute and State University; Blacksburg, VA USA;4.Department of Electrical and Computer Engineering; Virginia Polytechnic Institute and State University; Blacksburg, VA USA |
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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 interbud 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.Key words: stochastic phenotype, mitotic exit, non-genetic variability, cell cycle modeling, computational biology, stochastic modeling, deterministic modeling |
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