Dynamic Models of the Mitotic Cycle: Evidence for a Limit Cycle Oscillator

Control of the periodicity of mitosis, and maintenance of stable phase relation among events of the cell cycle, have been extensively studied in a number of prokaryotes (1,2) in tetrahymena (3,4) Paramecium (5), yeast (6), Physarum (7,8) and higher cells (9). Two broad classes of models have emerged over the past several decades (reviewed by J. M. Mitchison 10). The first envisions a recurrent sequence of discrete cellular events, related to one another as a simple causal loop sequence, or as partially independent, partially connected causal sequences eventually forming a loop. Hartwell’s (11) elegant genetic analysis of the yeast division cycle using temperature sensitive mutants stopping cells at specific phases has led him to this type of model. Such a causal loop model would explain both the periodicity of the cycle and the maintenance of proper phase relations between events of the cycle. The event; of the cycle are here considered as parts of the clock.