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When a budding yeast cell is unable to form a new bud, cell division pauses in G2 phase, either until a bud can grow or until the cell "adapts" to the situation by becoming dinucleate. Ciliberto et al. collected the available experimental data on this morphogenesis checkpoint, and on page 1243 they present a mathematical model that explains previous results and makes some surprising predictions.
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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.3 }5 z# K3 Q# n B' ?% \$ \
& J) X5 v& A& C$ @6 Z; }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.
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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.(Extra mass boosts the intermediate level) |
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发表于 2009-3-6 00:56
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