Time-keeping and Decision-making in the Cell Cycle

Abstract: Cell growth, DNA replication, mitosis and division are the fundamental processes by which life is passed on from one generation of eukaryotic cells to the next. The eukaryotic cell cycle is intrinsically a periodic process but not so much a ‘clock’ as a ‘copy machine’, making new daughter cells as warranted. Cells growing under ideal conditions divide with clock-like regularity; however, if they are challenged with DNA-damaging agents or mitotic spindle disruptors, they will not progress to the next stage of the cycle until the damage is repaired. These ‘decisions’ (to exit and re-enter the cell cycle) are essential to maintain the integrity of the genome from generation to generation. A crucial challenge for molecular cell biologists in the 1990s was to unravel the genetic and biochemical mechanisms of cell cycle control in eukaryotes. Central to this effort were biochemical studies of the clock-like regulation of ‘mitosis promoting factor’ during synchronous mitotic cycles of fertilized frog eggs and genetic studies of the switch-like regulation of ‘cyclin-dependent kinases’ in yeast cells. The complexity of these control systems demands a dynamical approach, as described in the first lecture. Using mathematical models of the control systems, I will uncover some of the secrets of cell cycle ‘clocks’ and ‘switches’.