QUANTITATIVE-ANALYSIS OF A MOLECULAR-MODEL OF MITOTIC CONTROL IN FISSION YEAST

A wealth of information has accumulated about the physiology, genetics and molecular biology of the cell cycle in the fission yeast, Schizos accharomyces pombe. From this information we have constructed a detail ed molecular mechanism of M-phase control based on the modification of M-phase promoting factor (MPF) by a suite of protein kinases (e.g. We e1 and Mik1 which inhibit MPF) and phosphatases (e.g. Cdc25 which acti vates MPF). In particular, we analyze the interphase checkpoint in S. pombe, where the wild-type cell confirms that S phase is complete and that the cell is large enough to finish the division cycle. In our mod el, incomplete DNA replication restrains the onset of M phase by inhib iting Cdc25 and activating Mik1, whereas increasing size biases the ce ll towards mitosis by down-regulating Wee1. By standard mathematical m ethods of chemical kinetics, we show that our model gives a quantitati vely accurate account of the effects of hydroxyurea treatments, nutrit ional shifts and other perturbations of the division cycle of wild-typ e and mutant cells.