Modeling the Budding Yeast Cell Cycle

GAL-CLB2 sic1∆

Simulation:

Change of parameters: ksb2'=0.12, ksc1'=ksc1"=0, MDT=150.

Experiments:

Toyn, J.H., Johnson, A.L., Donovan, J.D., Toone, W.M., Johnston, L.H. (1997). The Swi5 transcription factor of Saccharomyces cerevisiae has a role in exit from mitosis through induction of the cdk-inhibitor Sic1 in telophase. Genetics 145:85-96.
[Abstract] [Article]
Experimental results: Telophase arrest.
Comments: Problem for the model. It should be telophase arrested, but in simulation, it is inviable because division occurs in an unbudded cell.

In our simulation, deletion of SIC1 has little effect on the cyclic behaviour of Clb2 activity in GAL-CLB2 strains. Because Clb2 activates Cdc20, which in turn degrades Clb2, cells can tolerate quite high levels of Clb2 overproduction (Surana et al., 1993). Additional deletion of SIC1 just causes Cdc20 activation to start earlier and last longer, which is enough to negate the effect of higher Clb2 activity due to the absence of Sic1.

In the simulation, [BUD] never reaches 1 ([Bud]max=0.3), because high Clb2 kinase turns off SBF-dependent synthesis of Cln2. This failure should elicit inhibition of Clb2-kinase activity by the morphogenetic checkpoint (Lew, 2000; Ciliberto et al, 2003). A delay in the onset of mitosis may allow Clb2 to accumulate to such high levels that cells arrest in telophase.