DEVELOPING A MATHEMATICAL MODEL FOR THE FISSION YEAST CELL CYCLE: SIMULATING MUTANTS OVEREXPRESSING EITHER CDC25 OR WEE1
2006
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.
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