A
deterministic molecular model of the fission yeast cell cycle.
Akos Sveiczer (1),
Attila Csikasz-Nagy (1), John J. Tyson (2), Bela Novak (1)
(1) Dept Agricult Chem Technol, Budapest University Techn Econ, Szt. Gellert
ter 4, Budapest, H-1111, Hungary (asveiczer@mail.bme.hu); (2) Dept Biology,
Virginia Tech, Blacksburg, VA 24061, USA
Fission yeast is an attractive model and test organism in cell cycle research. Compared to baker's yeast, fission yeast has two important advantages. (i) It divides by symmetric medial fission, which enables good techniques of synchronization. (ii) The cylindrical shape cell grows exclusively at the tips with a constant diameter, so its age can be evaluated simply by its length. The main regulator of the G1/S phase transition in fission yeast is the transcription factor complex containing the Cdc10 protein. Cdc10 is known to be active from late mitosis up to the next S phase. It regulates the transcription of the main G1 cyclin (Cig2) and the main component of the licensing factor (Cdc18). However, Cig2 in complex with the Cdc2 protein kinase has a negative effect on Cdc10, causing a negative feedback loop in the regulation. Moreover, we hypothesize that Cdc10 also activates a proteolytic mechanism, which degrades two stabilisers of the G1 phase, the Rum1 and Ste9 proteins. Together with further ones, these biochemical reactions were converted into ordinary differential equations, and the simulation results correctly described the physiological behavior of wild-type cells and several cell-cycle mutants. The model explains why neither Rum1 nor Ste9 are essential in wild-type cycles, but why both are essential to block the cells in G1 phase in a cdc10 mutant. We can also simulate endoreplicative cycles (multiple S phases), which occur in the absence of the main G2 cyclin Cdc13.