The transition from mitosis into the first gap phase of the cell cycle in budding yeast is controlled by the Mitotic Exit Network (MEN). The network interprets spatiotemporal cues about the progression of mitosis and ensures that release of Cdc14 phosphatase occurs only after completion of key mitotic events. The MEN has been studied intensively; however, a unified understanding of how localisation and protein activity function together as a system is lacking. In this paper, we present a compartmental, logical model of the MEN that is capable of representing spatial aspects of regulation in parallel to control of enzymatic activity. We show that our model is capable of correctly predicting the phenotype of the majority of mutants we tested, including mutants that cause proteins to mislocalise. We use a continuous time implementation of the model to demonstrate that Cdc14 Early Anaphase Release (FEAR) ensures robust timing of anaphase, and we verify our findings in living cells. Furthermore, we show that our model can represent measured cell–cell variation in Spindle Position Checkpoint (SPoC) mutants. This work suggests a general approach to incorporate spatial effects into logical models. We anticipate that the model itself will be an important resource to experimental researchers, providing a rigorous platform to test hypotheses about regulation of mitotic exit.

出芽酵母从有丝分裂到细胞周期第一个间隙期的转变由有丝分裂出口网络 (MEN) 控制。该网络解释有关有丝分裂进程的时空线索，并确保仅在关键有丝分裂事件完成后才释放 Cdc14 磷酸酶。MEN 已经过深入研究；然而，缺乏对定位和蛋白质活性如何作为一个系统一起发挥作用的统一理解。在本文中，我们提出了 MEN 的分区逻辑模型，该模型能够表示与酶活性控制平行的调节的空间方面。我们表明我们的模型能够正确预测我们测试的大多数突变体的表型，包括导致蛋白质错误定位的突变体。我们使用该模型的连续时间实施来证明 Cdc14 早期后期释放 (FEAR) 可确保可靠的后期时间，并且我们验证了我们在活细胞中的发现。此外，我们表明我们的模型可以代表纺锤体位置检查点 (SPoC) 突变体中测量的细胞-细胞变异。这项工作提出了一种将空间效应纳入逻辑模型的通用方法。我们预计该模型本身将成为实验研究人员的重要资源，提供一个严格的平台来检验有关有丝分裂退出调节的假设。这项工作提出了一种将空间效应纳入逻辑模型的通用方法。我们预计该模型本身将成为实验研究人员的重要资源，提供一个严格的平台来检验有关有丝分裂退出调节的假设。这项工作提出了一种将空间效应纳入逻辑模型的通用方法。我们预计该模型本身将成为实验研究人员的重要资源，提供一个严格的平台来检验有关有丝分裂退出调节的假设。