146 CATALYZING INQUIRY
5.4.2.2 Cell Cycle Regulation,
Biological growth and reproduction depend ultimately on the cycle of DNA synthesis and physical
separation of the replicate DNA molecules within individual cells. In eukaryotes, these processes are
triggered by cyclin-dependent protein kinases (CDKs). In fission yeast, CDK activity (cdc2 = kinase
subunit, cdc13 = cyclin subunit) is regulated by a network of protein interactions (Figure 5.5), including
cyclin synthesis and degradation, phosphorylation of cdc2, and binding to an inhibitor.
A network of such complexity, with multiple feedback loops, cannot be understood thoroughly by
casual intuition. Instead, the network is converted into a set of nonlinear differential equations, and the
physiological implications of these equations are studied.^59 Numerical simulation of the equations
(Figure 5.6) provides complete time courses of every component and can be interpreted in terms of
observable events in the cell cycle. Simulations can be run, not only of wild-type cells but also of dozens
of mutants constructed by deleting or overexpressing each component singly or in multiple combina-
tions. From the observed phenotypes of these mutants it is possible to reverse-engineer the regulatory
network and the set of kinetic constants associated with the component reactions.
FIGURE 5.5 The cell-cycle control system in fission yeast. This system can be divided into three modules, which
regulate the transitions from G1 into S phase, from G2 into M phase, and exit from mitosis. SOURCE: J.J. Tyson, K.
Chen, and B. Novak, “Network Dynamics and Cell Physiology,” Nature Reviews of Molecular Cell Biology 2(12):908-
916, 2001. Figure and caption reproduced with permission from Nature Reviews of Molecular Cell Biology. Copyright
2001 Macmillan Magazines Ltd.
(^59) J.J. Tyson, K. Chen, and B. Novak, “Network Dynamics and Cell Physiology,” Nature Reviews: Molecular Cell Biology 2(12):908-
916, 2001; J.J. Tyson, A. Csikasz-Nagy, and B. Novak, “The Dynamics of Cell Cycle Regulation,” BioEssays 24(12):1095-1109, 2002.