Upon nitrogen starvation, Schizosaccharomyces pombe exit the mitotic cell cycle and become irreversibly committed to the completion of meiosis program. Meiotic cell divisions are coordinated with sporulation events to produce haploid spores. In the last few decades, experiments on fission yeast have revealed different molecular players involved in two meiotic cell divisions, meiosis I (MI) and meiosis II (MII). How the MI entry, MI-to-MII transition, and MII exit occur because of the dynamics of the regulatory network is not well understood. In this work, we developed a comprehensive mathematical model of the network that describes the temporal dynamics of meiotic progression. The model accounts for the phenotypes of several experimental data (single and multiple mutations). We demonstrate the control strategy involving multiple feedback loops to yield two successive division cycles. The differential regulation of anaphase-promoting complex/cyclosome (APC/C) coactivators and its inhibitors is crucial for the dynamics of both MI-to-MII transition and MII exit. This model generates mechanistic insights that help in further experiments and modeling.

中文翻译：

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模拟减数分裂细胞分裂的控制：进入、进行和退出

在氮饥饿时，粟酒裂殖酵母退出有丝分裂细胞周期并不可逆转地致力于完成减数分裂程序。减数分裂细胞分裂与孢子形成事件协调以产生单倍体孢子。在过去的几十年里，裂殖酵母的实验揭示了参与两个减数分裂细胞分裂的不同分子参与者，减数分裂 I (MI) 和减数分裂 II (MII)。由于监管网络的动态变化，MI 进入、MI 到 MII 的转换和 MII 退出是如何发生的，目前尚不清楚。在这项工作中，我们开发了一个全面的网络数学模型，该模型描述了减数分裂进程的时间动态。该模型解释了几个实验数据（单突变和多突变）的表型。我们演示了涉及多个反馈回路的控制策略，以产生两个连续的除法周期。后期促进复合物/环体 (APC/C) 共激活剂及其抑制剂的差异调节对于 MI 到 MII 过渡和 MII 退出的动力学至关重要。该模型生成有助于进一步实验和建模的机械见解。