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Vol. 13, Issue 1, 52-70, January 2002
The Rockefeller University, New York, New
York 10021
We derived novel, testable predictions from a
mathematical model of the budding yeast cell cycle. A
key qualitative prediction of bistability was confirmed in a
strain simultaneously lacking cdc14 and G1
cyclins. The model correctly predicted quantitative dependence of cell size on gene dosage of the G1 cyclin
CLN3, but it incorrectly predicted strong
genetic interactions between G1 cyclins and the anaphase-
promoting complex specificity factor Cdh1. To provide
constraints on model generation, we determined accurate
concentrations for the abundance of all nine
cyclins as well as the inhibitor Sic1 and the catalytic
subunit Cdc28. For many of these we determined abundance
throughout the cell cycle by centrifugal elutriation, in the
presence or absence of Cdh1. In addition, perturbations to
the Clb-kinase oscillator were introduced, and the effects
on cyclin and Sic1 levels were compared between model and
experiment. Reasonable agreement was obtained in many of
these experiments, but significant experimental discrepancies from the model predictions were also observed.
Thus, the model is a strong but incomplete attempt at a
realistic representation of cell cycle control. Constraints
of the sort developed here will be important in development
of a truly predictive model.
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