Testing a mathematical model of the yeast cell cycle
Testing a mathematical model of the yeast cell cycle
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DOI：
10.1091/mbc.01-05-0265
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发表时间：
2002-01-01
影响因子：
3.3
通讯作者：
Klovstad, M
中科院分区：
文献类型：
--
作者：
Cross, FR;Archambault, V;Klovstad, M
我们从芽殖酵母细胞周期的数学模型中得出了新颖的、可检验的预测。在同时缺乏cdc 14和G1细胞周期蛋白的菌株中证实了双稳态的关键定性预测。该模型正确地预测了细胞大小对G1细胞周期蛋白CLN 3基因剂量的定量依赖性，但它错误地预测了G1细胞周期蛋白和后期促进复杂特异性因子Cdh 1之间的强遗传相互作用。为了提供对模型生成的限制，我们确定了所有9种细胞周期蛋白以及抑制剂Sic 1和催化亚基Cdc 28丰度的准确浓度。对于许多这些，我们确定了丰度在整个细胞周期的离心淘洗，在Cdh 1的存在或不存在。此外，还引入了对Clb-激酶振荡器的扰动，并比较了模型和实验对cyclin和Sic 1水平的影响。在许多这些实验中获得了合理的一致性，但也观察到与模型预测的显着实验差异。因此，该模型是一个强大的，但不完整的尝试，在一个现实的代表性细胞周期控制。在这里开发的这类约束对于开发一个真正的预测模型是很重要的。
We derived novel, testable predictions from a mathematical model of the budding yeast cell cycle. A key qualitative prediction of bistability was confirmed in a strain simultaneously lacking cdc14 and G1 cyclins. The model correctly predicted quantitative dependence of cell size on gene dosage of the G1 cyclin CLN3, but it incorrectly predicted strong genetic interactions between G1 cyclins and the anaphase-promoting complex specificity factor Cdh1. To provide constraints on model generation, we determined accurate concentrations for the abundance of all nine cyclins as well as the inhibitor Sic1 and the catalytic subunit Cdc28. For many of these we determined abundance throughout the cell cycle by centrifugal elutriation, in the presence or absence of Cdh1. In addition, perturbations to the Clb-kinase oscillator were introduced, and the effects on cyclin and Sic1 levels were compared between model and experiment. Reasonable agreement was obtained in many of these experiments, but significant experimental discrepancies from the model predictions were also observed. Thus, the model is a strong but incomplete attempt at a realistic representation of cell cycle control. Constraints of the sort developed here will be important in development of a truly predictive model.