DEVELOPING A MATHEMATICAL MODEL FOR THE FISSION YEAST CELL CYCLE: SIMULATING MUTANTS OVEREXPRESSING EITHER CDC25 OR WEE1

Abstract

During the last decade several mathematical models were constructed to describe the fission yeast cell cycle. In these models, fluctuations of MPF activity were responsible for cell cycle transitions, and they successfully explained the behaviour of wild-type fission yeast cells and many cell division cycle mutants as well. However, the mutants involved in these models were mainly loss-of-function mutants (either temperature-sensitive point mutants or gene deletion ones). By contrast, the phenotypes of several gene overproducing (op) mutants have been published during the last twenty years, like those of cdc25^op and wee1^op cells (in the case of the latter one, even the effects of different overexpression levels are known). Since Wee1 and Cdc25 is a kinase-phosphatase pair, regulating MPF activity and as a consequence, timing mitotic onset in fission yeast, a detailed mathematical model of the fission yeast cell cycle should be able to simulate these overexpression mutants. Within the framework of this paper, a formerly published model was tested for these mutants. In order to describe properly the behaviour of cdc25^op and wee1^op mutants, some alterations had to be made in the original model, both in the parameter values and in the equations. If these corrections have been involved, the newly developed model also maintained its capability to explain the phenotypes of all those mutants, for which the original model was made. Furthermore, the model predicts the phenotypes of two mutants not yet constructed by geneticists.