DNA replication and mitotic entry: A brake model for cell cycle progression

J Cell Biol. 2019 Dec 2;218(12):3892-3902. doi: 10.1083/jcb.201909032. Epub 2019 Nov 11.


The core function of the cell cycle is to duplicate the genome and divide the duplicated DNA into two daughter cells. These processes need to be carefully coordinated, as cell division before DNA replication is complete leads to genome instability and cell death. Recent observations show that DNA replication, far from being only a consequence of cell cycle progression, plays a key role in coordinating cell cycle activities. DNA replication, through checkpoint kinase signaling, restricts the activity of cyclin-dependent kinases (CDKs) that promote cell division. The S/G2 transition is therefore emerging as a crucial regulatory step to determine the timing of mitosis. Here we discuss recent observations that redefine the coupling between DNA replication and cell division and incorporate these insights into an updated cell cycle model for human cells. We propose a cell cycle model based on a single trigger and sequential releases of three molecular brakes that determine the kinetics of CDK activation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Cycle Checkpoints*
  • Cell Cycle Proteins / metabolism
  • Cell Division
  • Cell Proliferation
  • Cyclin-Dependent Kinases / metabolism
  • DNA Damage
  • DNA Replication*
  • Enzyme Activation
  • Humans
  • Kinetics
  • Mice
  • Mitosis*
  • Signal Transduction


  • Cell Cycle Proteins
  • Cyclin-Dependent Kinases