Cell Cycle, DNA replication and Cell Division
Stanford Univeristy, School of Medicine
Department of Chemical and Systems Biology
Ferrell, James E.
Mitosis and meiosis are certainly among the most spectacular events in all of biology. These processes are brought about by protein kinase complexes consisting of the cyclin-dependent kinase CDK1 (also called Cdc2) and a mitotic cyclin (in animals, an A-type cyclin or a B-type cyclin). The abrupt activation of cyclin-CDK1 at the onset of mitosis, and the abrupt inactivation of cyclin-CDK1 at the metaphase/anaphase transition near the end of mitosis, constitute the climax of the cell cycle and result in the division of one cell into two. In some circumstances, the eukaryotic cell cycle can be best described as a succession of contingent events. For example, in most somatic cells in culture, cell growth is followed by DNA replication, then more cell growth, then mitotic entry and chromosome congression, then sister chromatid separation and mitotic exit. Entry into a new phase of the cell cycle may depend upon the successful completion of some important event in the previous phase. E.g., the cell cannot begin DNA replication until sufficient growth has occurred, cannot enter mitosis until DNA replication is completed, and cannot initiate sister chromatid separation until congression is achieved. In other contexts the cell cycle is better described as an autonomous oscillation. For example, in the early Xenopus embryo, every ~30 minutes CDK1 is activated and this reliable rhythm is maintained even if DNA replication or mitosis is blocked. We have been studying the system of regulatory proteins that drives the cell cycle, through a combination of quantitative experimental approaches, computational modeling, and the theory of nonlinear dynamics. Our goal is to understand the design principles of this system, and perhaps to gain insight into the systems that drive other biological oscillations (e.g. heart beats, cal