Mathematical model of the fission yeast cell cycle with checkpoint controls at the G1/S, G2/M and metaphase/anaphase transitions
Mathematical model of the fission yeast cell cycle with checkpoint controls at the G1/S, G2/M and metaphase/anaphase transitions
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DOI：
10.1016/s0301-4622(98)00133-1
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发表时间：
1998-05-05
影响因子：
3.8
通讯作者：
Tyson, JJ
中科院分区：
文献类型：
--
作者：
Novak, B;Csikasz-Nagy, A;Tyson, JJ
裂殖酵母细胞周期的所有事件都可以通过单个细胞周期蛋白依赖性蛋白激酶（Cdc13/Cdc2 异二聚体）的波动来协调。 G1/S 转变由 Cdc13/Cdc2 及其化学计量抑制剂 Rum1 的相互作用控制。 G2/M 转变由激酶磷酸酶对 Wee1 和 Cdc25 调节，它们决定 Cdc2 的 Tyr-15 残基的磷酸化状态。中期/后期转变由 Cdc13/Cdc2 和后期促进复合物之间的相互作用控制，后者标记 Cdc13 亚基进行蛋白水解。我们构建了裂殖酵母生长和分裂的数学模型，其中包含所有三个关键的检查点控制。通过数值模拟，我们表明该模型与细胞周期突变体的广泛选择一致，并且我们预测了几种尚未构建的多突变体菌株的表型。 (C) 1998 Elsevier Science B.V. 保留所有权利。
All events of the fission yeast cell cycle can be orchestrated by fluctuations of a single cyclin-dependent protein kinase, the Cdc13/Cdc2 heterodimer. The G1/S transition is controlled by interactions of Cdc13/Cdc2 and its stoichiometric inhibitor, Rum1. The G2/M transition is regulated by a kinase-phosphatase pair, Wee1 and Cdc25, which determine the phosphorylation state of the Tyr-15 residue of Cdc2. The meta/anaphase transition is controlled by interactions between Cdc13/Cdc2 and the anaphase promoting complex, which labels Cdc13 subunits for proteolysis. We construct a mathematical model of fission yeast growth and division that encompasses all three crucial checkpoint controls. By numerical simulations we show that the model is consistent with a broad selection of cell cycle mutants, and we predict the phenotypes of several multiple-mutant strains that have not yet been constructed. (C) 1998 Elsevier Science B.V. All rights reserved.