BIOPHYSICAL THEORY AND MODELING |
Analysis of a generic model of eukaryotic cell cycle
regulation
Attila Csikasz-Nagy 1, Dorjsuren Battogtokh 2, Katherine C. Chen 2, Bela Novak 3 and John J. Tyson 4*
1 Budapest Univ Techn & Econ
2 Virginia Tech
3 Budapest Univ. Techn & Econ.
4 Virginia Polytechnic Institute
* To whom correspondence should be addressed. E-mail: tyson{at}vt.edu.
Submitted on January 12, 2006
Revised on February 20, 2006
Accepted on 16 March 2006
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Abstract |
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We propose a protein interaction network for the regulation of DNA synthesis and mitosis that emphasizes the universality of the regulatory system among eukaryotic cells. The idiosyncrasies of cell cycle regulation in particular organisms can be attributed, we claim, to specific settings of rate constants in the dynamic network of chemical reactions. The values of these rate constants are determined ultimately by the genetic makeup of an organism. To support these claims, we convert the reaction mechanism into a set of governing kinetic equations and provide parameter values (specific to budding yeast, fission yeast, frog eggs and mammalian cells) that account for many curious features of cell cycle regulation in these organisms. Using one-parameter bifurcation diagrams, we show how overall cell growth drives progression through the cell cycle, how cell-size homeostasis can be achieved by two different strategies, and how mutations remodel bifurcation diagrams and create unusual cell-division phenotypes. The relation between gene dosage and phenotype can be summarized compactly in two-parameter bifurcation diagrams. Our approach provides a theoretical framework in which to understand both the universality and particularity of cell cycle regulation, and to construct, in modular fashion, increasingly complex models of the networks controlling cell growth and division.
Key Words:
bifurcation theory, cyclin-dependent kinase, regulatory network, systems biology
