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,Schizosaccharomyces pombe.From this information we have constructed a detailed molecular mechanism of M-phase control based on the modification of M-phase promoting factor (MPF) by a suite of protein kinases (e.g. Weel and Mikl which inhibit MPF) and phosphatases (e.g. Cdc25 which activates MPF). In particular, we analyze the interphase checkpoint inS. 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 model, incomplete DNA replication restrains the onset of M phase by inhibiting Cdc25 and activating Mikl, whereas increasing size biases the cell towards mitosis by down-regulating Weel. By standard mathematical methods of chemical kinetics, we show that our model gives a quantitatively accurate account of the effects of hydroxyurea treatments, nutritional shifts and other perturbations of the division cycle of wild-type and mutant cells.