Modeling Controls and Variability of the Cell Cycle

Cell cycle events (initiation of DNA replication, length of the G₂ phase, occurrence of mitosis and of cell division) follow temporal patterns which are characteristic of each cell type and growth condition, thus suggesting the existence of complex control mechanisms /1,2/. While considerable progress as been made in the description of macromolecular syntheses which characterize different growth conditions, our knowledge on the regulatory mechanisms that coordinate growth with nuclear and cell division is still poor. Clearly the reductionistic approach, which has been so useful for the description of the molecular components of a cell and of the more simple regulatory systems (regulation of enzymatic pathways, control of gene expression in bacteria), is not adequate for the study of highly integrated systems, such those controlling growth and cell division, for which it seems necessary to develop an integrated approach. Mathematical models may well be useful for this undertaking. In fact, they allow quantitative description of both the interrelations among the relevant variables of the phenomenon and the dynamics of the events under consideration. Many mathematical models have been developed in order to describe the dynamics of the cycle events, and their analytical solutions and the simulations, which are often required for a more accurate analysis of their predictions, may help to better understand the regulatory mechanisms of cell proliferation. Comparison of the predictions of the model with experimental results allows verification of the validity of the assumed functional or causal links.