From START to FINISH: computational analysis of cell cycle control in budding yeast
From START to FINISH: computational analysis of cell cycle control in budding yeast
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DOI：
10.1038/npjsba.2015.16
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发表时间：
2015-01-01
影响因子：
4
通讯作者：
Tyson, John J.
中科院分区：
文献类型：
--
作者：
Kraikivski, Pavel;Chen, Katherine C.;Tyson, John J.
在芽殖酵母的细胞分裂周期中，START指的是一系列紧密相连的事件，这些事件使细胞为芽殖和DNA复制做好准备，FINISH指的是细胞退出有丝分裂并分裂成母细胞和子细胞的相关事件。基于分子生物学家在表征控制START和FINISH的基因和蛋白质方面取得的最新进展，我们构建了一个新的酵母细胞周期进程数学模型。我们的模型利用细胞周期控制网络中时间尺度的自然分离来构建蛋白质合成和降解、翻译后修饰以及多聚体复合物的快速形成和解离的微分代数方程系统。该模型提供了一个统一的帐户观察到的表型的257个突变酵母菌株（98%的数据集中的263株用于约束模型）。然后，我们使用该模型来预测30种新的突变等位基因组合的表型。我们的综合模型的分子事件控制细胞周期进程的芽殖酵母既有解释力和预测力。未来的实验测试模型的预测将是有用的，以完善潜在的分子机制，约束模型的可调参数，并提供新的见解如何在芽殖酵母细胞分裂周期的调节。
In the cell division cycle of budding yeast, START refers to a set of tightly linked events that prepare a cell for budding and DNA replication, and FINISH denotes the interrelated events by which the cell exits from mitosis and divides into mother and daughter cells. On the basis of recent progress made by molecular biologists in characterizing the genes and proteins that control START and FINISH, we crafted a new mathematical model of cell cycle progression in yeast. Our model exploits a natural separation of time scales in the cell cycle control network to construct a system of differential-algebraic equations for protein synthesis and degradation, post-translational modifications, and rapid formation and dissociation of multimeric complexes. The model provides a unified account of the observed phenotypes of 257 mutant yeast strains (98% of the 263 strains in the data set used to constrain the model). We then use the model to predict the phenotypes of 30 novel combinations of mutant alleles. Our comprehensive model of the molecular events controlling cell cycle progression in budding yeast has both explanatory and predictive power. Future experimental tests of the model's predictions will be useful to refine the underlying molecular mechanism, to constrain the adjustable parameters of the model, and to provide new insights into how the cell division cycle is regulated in budding yeast.