Typically cells replicate their genome only once per division cycle, but under some circumstances, both natural and unnatural, cells synthesize an overabundance of DNA, either in a disorganized fashion (‘over-replication’) or by a systematic doubling of chromosome number (‘endoreplication’). These variations on the theme of DNA replication and division have been studied in strains of fission yeast, Schizosaccharomyces pombe, carrying mutations that interfere with the function of mitotic cyclin-dependent kinase (Cdk1:Cdc13) without impeding the roles of DNA-replication loading-factor (Cdc18) and S-phase cyclin-dependent kinase (Cdk1:Cig2). Some of these mutations support endoreplication, and some over-replication. In this paper, we propose a dynamical model of the interactions among the proteins governing DNA replication and cell division in fission yeast. By computational simulations of the mathematical model, we account for the observed phenotypes of these re-replicating mutants, and by theoretical analysis of the dynamical system, we provide insight into the molecular distinctions between over-replicating and endoreplicating cells. In case of induced over-production of regulatory proteins, our model predicts that cells first switch from normal mitotic cell cycles to growth-controlled endoreplication, and ultimately to disorganized over-replication, parallel to the slow increase of protein to very high levels.

通常，细胞每个分裂周期只复制一次基因组，但在某些情况下，无论是自然的还是非自然的，细胞都会以杂乱无章的方式（“过度复制”）或通过染色体数量的系统加倍（“内复制'）。已经在裂殖酵母、粟酒裂殖酵母菌株中研究了这些关于 DNA 复制和分裂主题的变异，携带干扰有丝分裂细胞周期蛋白依赖性激酶 (Cdk1:Cdc13) 功能的突变，而不妨碍 DNA 复制加载因子 (Cdc18) 和 S 期细胞周期蛋白依赖性激酶 (Cdk1:Cig2) 的作用。这些突变中的一些支持内复制，一些支持过度复制。在本文中，我们提出了一个关于裂殖酵母中控制 DNA 复制和细胞分裂的蛋白质之间相互作用的动力学模型。通过数学模型的计算模拟，我们解释了这些重复复制突变体的观察表型，并通过动态系统的理论分析，我们深入了解了过度复制和内复制细胞之间的分子差异。在诱导过度生产调节蛋白的情况下，