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Vol. 15, Issue 8, 3841-3862, August 2004
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* Department of Biology, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061-0406;
Molecular Network Dynamics Research Group of the Hungarian Academy of Sciences and Department of Agricultural and Chemical Technology, Budapest University of Technology and Economics, H-1521 Budapest, Hungary; and
The Rockefeller University, New York, New York 10021
Submitted November 7, 2003;
Revised May 3, 2004;
Accepted May 15, 2004
Monitoring Editor: Thomas Pollard
The adaptive responses of a living cell to internal and external signals are controlled by networks of proteins whose interactions are so complex that the functional integration of the network cannot be comprehended by intuitive reasoning alone. Mathematical modeling, based on biochemical rate equations, provides a rigorous and reliable tool for unraveling the complexities of molecular regulatory networks. The budding yeast cell cycle is a challenging test case for this approach, because the control system is known in exquisite detail and its function is constrained by the phenotypic properties of >100 genetically engineered strains. We show that a mathematical model built on a consensus picture of this control system is largely successful in explaining the phenotypes of mutants described so far. A few inconsistencies between the model and experiments indicate aspects of the mechanism that require revision. In addition, the model allows one to frame and critique hypotheses about how the division cycle is regulated in wild-type and mutant cells, to predict the phenotypes of new mutant combinations, and to estimate the effective values of biochemical rate constants that are difficult to measure directly in vivo.
Abbreviations used: CKI, cyclin-dependent kinase inhibitor; MDT, mass doubling time.
Online version of this article contains supporting material. Online version is available at www.molbiolcell.org.
Corresponding authors. E-mail addresses: tyson{at}vt.edu or kchen{at}vt.edu.
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