An Autonomous Oscillation Times and Executes Centriole Biogenesis

Cell. 2020 Jun 25;181(7):1566-1581.e27. doi: 10.1016/j.cell.2020.05.018. Epub 2020 Jun 11.


The accurate timing and execution of organelle biogenesis is crucial for cell physiology. Centriole biogenesis is regulated by Polo-like kinase 4 (Plk4) and initiates in S-phase when a daughter centriole grows from the side of a pre-existing mother. Here, we show that a Plk4 oscillation at the base of the growing centriole initiates and times centriole biogenesis to ensure that centrioles grow at the right time and to the right size. The Plk4 oscillation is normally entrained to the cell-cycle oscillator but can run autonomously of it-potentially explaining why centrioles can duplicate independently of cell-cycle progression. Mathematical modeling indicates that the Plk4 oscillation can be generated by a time-delayed negative feedback loop in which Plk4 inactivates the interaction with its centriolar receptor through multiple rounds of phosphorylation. We hypothesize that similar organelle-specific oscillations could regulate the timing and execution of organelle biogenesis more generally.

Keywords: FCS; biological oscillator; biological timing; cell cycle; centriole; centriole duplication; centrosome; organelle biogenesis; organelle sizing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Clocks / physiology*
  • Cell Cycle / physiology
  • Cell Cycle Proteins / metabolism
  • Centrioles / metabolism*
  • Centrosome / metabolism
  • Drosophila Proteins / metabolism*
  • Drosophila Proteins / physiology
  • Drosophila melanogaster / metabolism
  • Organelle Biogenesis
  • Phosphorylation
  • Protein Serine-Threonine Kinases / metabolism*
  • Protein Serine-Threonine Kinases / physiology


  • Cell Cycle Proteins
  • Drosophila Proteins
  • Protein Serine-Threonine Kinases
  • Sak protein, Drosophila