Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, IL 60637.
Institute for Biophysical Dynamics, University of Chicago, Chicago, IL 60637.
Proc Natl Acad Sci U S A. 2021 May 18;118(20). doi: 10.1073/pnas.2022516118.
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 , 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体能下降，而且来自多种生物的证据表明，生物钟的破坏会导致细胞周期失调。然而，昼夜节律调节对 DNA 复制这一基本过程的功能仍然难以捉摸。在这里，我们证明在蓝细菌中，一种具有最简单已知生物钟振荡器的模式生物中，生物钟会产生 DNA 复制的节律，以最大限度地减少黄昏时分接近黄昏时必须在日落之后完成的开放复制叉的数量。时钟产生的代谢节律确保了夜间早期有可用的资源来支持任何剩余的复制叉。通过数学建模和实验，我们表明，由于时钟-环境失配引起的代谢缺陷会导致复制体在黑暗中过早解体和复制中止，使细胞留下不完整的染色体，这些染色体在夜间持续存在。因此，我们的研究表明，这种古老的生物钟在蓝细菌中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。
