"Math models morphogenesis and mitosis".
Alan W. Dove
The morphogenesis checkpoint relies on antagonism between the Swe1
kinase, which inhibits entry into mitosis, and the active form of the Cdc28–Clb2
cyclin complex, which promotes it. In the model, a set of differential
equations accounts for the phenotypes of a dozen morphogenesis checkpoint
mutants by incorporating a few initial assumptions. Although previous work
showed that Hsl1 kinase flags Swe1 for degradation, the mathematical model
demonstrates that Hsl1 must also indirectly inhibit Swe1 activity.
Extra mass boosts the intermediate level of Cdc2 activity to induce mitosis.
The model also illuminates adaptation. Numerical simulation shows that small cells keep Cdc28–Clb2 activity at a low steady-state level, but at a critical cell size, Cdc28–Clb2 activity abandons the steady-state and enters an oscillatory regime. Normally, a single oscillation ends in mitosis, producing two smaller cells that are reset to the low steady-state leve. But when bud formation is impaired, the morphogenesis checkpoint enforces an intermediate steady-state level of Cdc28 kinase activity. At this level, DNA synthesis proceeds, but cells pause in G2. Once these arrested cells reach a second critical size threshold, they bypass the morphogenesis checkpoint and enter the Cdc28–Clb2 oscillatory state, dividing their nuclei.
The morphogenesis checkpoint seems to raise the size threshold for progression of the cell cycle. The model predicts that once that threshold is passed in the absence of bud formation, the mitotic cycle should continue unchecked, and the next cycle should be faster. Testing these predictions should further refine the model.
Mathematical model of the morphogenesis checkpoint in budding yeast
Andrea Ciliberto, Bela Novak, and John
J. Tyson
JCB 2003 163:
1243-1254.
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euchromatin: "the most active portion of the genome within the cell nucleus".