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Vol. 16, Issue 5, 2129-2138, May 2005

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Quantitative Characterization of a Mitotic Cyclin Threshold Regulating Exit from Mitosis

Frederick R. Cross ^*, Lea Schroeder ^*, Martin Kruse ^* , and Katherine C. Chen 

^* The Rockefeller University, New York, NY 10021; Department of Biology, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061-0406

Submitted October 14, 2004; Accepted January 24, 2005
Monitoring Editor: Mark Solomon

Regulation of cyclin abundance is central to eukaryotic cell cycle control. Strong overexpression of mitotic cyclins is known to lock the system in mitosis, but the quantitative behavior of the control system as this threshold is approached has only been characterized in the in vitro Xenopus extract system. Here, we quantitate the threshold for mitotic block in budding yeast caused by constitutive overexpression of the mitotic cyclin Clb2. Near this threshold, the system displays marked loss of robustness, in that loss or even heterozygosity for some regulators becomes deleterious or lethal, even though complete loss of these regulators is tolerated at normal cyclin expression levels. Recently, we presented a quantitative kinetic model of the budding yeast cell cycle. Here, we use this model to generate biochemical predictions for Clb2 levels, asynchronous as well as through the cell cycle, as the Clb2 overexpression threshold is approached. The model predictions compare well with biochemical data, even though no data of this type were available during model generation. The loss of robustness of the Clb2 overexpressing system is also predicted by the model. These results provide strong confirmation of the model's predictive ability.

Present address: Bernhard-Nocht-Institute for Tropical Medicine, AG Wiese, Bernhard-Nocht-Strasse 74, 20359 Hamburg, Germany.

Address correspondence to: Frederick R. Cross (fcross{at}rockefeller.edu).

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