4.4 Review

Time-keeping and decision-making in the cell cycle

期刊

INTERFACE FOCUS
卷 12, 期 4, 页码 -

出版社

ROYAL SOC
DOI: 10.1098/rsfs.2021.0075

关键词

cell cycle regulation; cell cycle checkpoints; cyclin-dependent kinases; mathematical models; limit cycles; bistable switches

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资金

  1. BBSRC Strategic LoLa grant [BB/M00354X/1]

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Cell growth, DNA replication, mitosis, and division are fundamental processes for passing on life. The eukaryotic cell cycle is a periodic process that plays a crucial role in maintaining the integrity of the genome. Key factors in cell cycle control include mitosis promoting factor and cyclin-dependent kinases.
Cell growth, DNA replication, mitosis and division are the fundamental processes by which life is passed on from one generation of eukaryotic cells to the next. The eukaryotic cell cycle is intrinsically a periodic process but not so much a 'clock' as a 'copy machine', making new daughter cells as warranted. Cells growing under ideal conditions divide with clock-like regularity; however, if they are challenged with DNA-damaging agents or mitotic spindle disrupters, they will not progress to the next stage of the cycle until the damage is repaired. These 'decisions' (to exit and re-enter the cell cycle) are essential to maintain the integrity of the genome from generation to generation. A crucial challenge for molecular cell biologists in the 1990s was to unravel the genetic and biochemical mechanisms of cell cycle control in eukaryotes. Central to this effort were biochemical studies of the clock-like regulation of 'mitosis promoting factor' during synchronous mitotic cycles of fertilized frog eggs and genetic studies of the switch-like regulation of 'cyclin-dependent kinases' in yeast cells. In this review, we uncover some secrets of cell cycle regulation by mathematical modelling of increasingly more complex molecular regulatory networks of cell cycle 'clocks' and 'switches'.

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