Modeling the Budding Yeast Cell Cycle

sic1∆ cdh1∆

Simulation:

Change of parameters: ksc1'=ksc1"=0, kscdh=0, init CDH1T=CDH1=0.

Experiments:

Schwab, M., Lutum, A.S. and Seufert, W. (1997). Yeast Hct1 is a regulator of Clb2 cyclin proteolysis. Cell 90:683-693.
[Abstract] [Article]
Visintin, R., Prinz, S. and Amon, A. (1997). CDC20 and CDH1: a family of substrate-specific activators of APC-dependent proteolysis. Science 278:460-463.
[Abstract] [Article]
Wasch, R. and Cross, F. (2002). APC-dependent proteolysis of the mitotic cyclin Clb2 is essential for mitotic exit. Nature 418:556-562.
[Abstract] [Article]
Archambault, V., Li, C.X., Tackett, A.J., Wasch, R., Chait, B.T., Rout, M.P. and Cross, F.R. (2003). Genetic and biochemical evaluation of the importance of Cdc6 in regulating mitotic exit. Mol. Biol. Cell 14:4592-4604.
[Abstract] [Article]
Experimental results: Able to exit mitosis with high Clb2-kinase activity.

(1) Schwab: inviable. The 'sic1∆ cdh1∆' double mutant spores germinated, went through a single round of division and arrested as large budded cells, consistent with a block in mitosis in the second cycle.

(2) Visintin: inviable. The double mutant spores germinated but arrested as large budded cells after 1-3 cycles.

(3) Wasch and Cross: inviable. Fig. 3, these mutants are able to exit from the first mitosis, arresting (not uniformly) in the next cycle with replicated (but un-separated) DNA, and short spindles. They are not telophase arrested. Their phenotype is similar to those of the mutant strain CLB5-db∆ sic1∆, which is shown (their Fig. 2) to have a high frequency for plasmid loss, suggesting that they have problems in origin licensing.
Comments: Problem for the model. In our simulation, it appears to be viable. However, [BUD] never reaches 1 after the first cycle.

In our simulation, the double mutant is able to complete the first cycle, and to initiate DNA synthesis and undergoes nuclear division, but it cannot form a bud from the second cycle on ([Bud]max < 0.28), because SBF cannot be activated due to the ever present high Clb2 activity.

See the Target model for more discussion on this mutant and how to modify the model to accommodate it.