Disruption of circadian rhythms causes decreased health and fitness, and evidence from multiple organisms links clock disruption to dysregulation of the cell cycle. However, the function of circadian regulation for the essential process of DNA replication remains elusive. Here, we demonstrate that in the cyanobacterium Synechococcus elongatus, a model organism with the simplest known circadian oscillator, the clock generates rhythms in DNA replication to minimize the number of open replication forks near dusk that would have to complete after sunset. Metabolic rhythms generated by the clock ensure that resources are available early at night to support any remaining replication forks. Combining mathematical modeling and experiments, we show that metabolic defects caused by clock–environment misalignment result in premature replisome disassembly and replicative abortion in the dark, leaving cells with incomplete chromosomes that persist through the night. Our study thus demonstrates that a major function of this ancient clock in cyanobacteria is to ensure successful completion of genome replication in a cycling environment.

昼夜节律的破坏会导致健康和健康状况下降，并且来自多种生物体的证据将时钟破坏与细胞周期失调联系起来。然而，昼夜节律对 DNA 复制基本过程的调节功能仍然难以捉摸。在这里，我们证明在蓝藻Synechococcus elongatus中，一种具有最简单的已知昼夜节律振荡器的模型生物，时钟在 DNA 复制中产生节律，以最大限度地减少必须在日落后完成的黄昏附近开放复制叉的数量。时钟产生的代谢节律确保资源在深夜可用以支持任何剩余的复制叉。结合数学建模和实验，我们表明，由时钟-环境失调引起的代谢缺陷会导致复制体过早分解和黑暗中的复制流产，从而使染色体不完整的细胞持续整夜。因此，我们的研究表明，蓝藻中这个古老时钟的一个主要功能是确保在循环环境中成功完成基因组复制。