Modeling the Budding Yeast Cell Cycle

cdh1∆

Simulation:

Change of parameters: kscdh=0, init CDH1T=CDH1=0.
Length of G1 phase: 66.3 min.
Mass at division: 1.91

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]
Jorgensen, P., Nishikawa, J.L., Breitkreutz, B.J. and Tyers, M. (2002). Systematic identification of pathways that couple cell growth and division in yeast. Science 297:395-400.
[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]
Experimental results: Schwab and Cross: Viable, Clb2 level high throughout the cell cycle.
Jorgensen: Fig. 2 & Table 1. cdh1∆ mutant is viable but smaller than WT. It is born at a smaller size (24 fL for WT and 14fL for cdh1∆), it grows slower (MDT is 87 min for WT and 115 min for the mutant), and buds at a smaller size (the critical size for budding is 32 fL for WT and 27 fL for the mutant).
Comments: Problem for the model. Although the model predicts correctly that the mutant cells are viable and small (73% wild type size), it does not account for early budding or slower growth rate.

Slower growth rate indicates some effect of Cdh1 on nutrient uptake or proteinsynthesis, which the model does not consider. Early budding of cdh1∆ cells suggests that Cdh1 is inhibitory for START: it may target some yet-unidentified activator of START for ubiquitin-dependent proteolysis. The known Cdh1 targets (Clb2, Cdc20, Cdc5) do not satisfy this requirement, they are all inhibitors START: Clb2 turns off SBF, Cdc20 degrades Clb5, and Cdc5 activates Cdc14 release, which in turn activates Sic1 synthesis.