Polo-like kinase-1 controls recovery from a G2 DNA damage-induced arrest in mammalian cells

Mol Cell. 2004 Sep 10;15(5):799-811. doi: 10.1016/j.molcel.2004.07.015.


DNA damage triggers multiple checkpoint pathways to arrest cell cycle progression. Less is known about the mechanisms that allow resumption of the cell cycle once checkpoint signaling is silenced. Here we show that while in undamaged cells several redundant pathways can promote the onset of mitosis, this redundancy is lost in cells recovering from a DNA damage-induced arrest. We demonstrate that Plk1 is crucial for mitotic entry following recovery from DNA damage. However, Plk1 is no longer required in cells depleted of Wee1, and we could show that Plk1 is involved in the degradation of Wee1 at the onset of mitosis. Thus, our data show that the cell cycle machinery is reset in response to DNA damage and that cells become critically dependent on Plk1-mediated degradation of Wee1 for their recovery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cell Line, Tumor
  • DNA Damage / genetics*
  • G2 Phase / genetics
  • G2 Phase / physiology*
  • Genes, cdc / physiology*
  • Humans
  • Mitosis / genetics
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Protein Kinases / genetics
  • Protein Kinases / metabolism*
  • Protein-Serine-Threonine Kinases
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / metabolism*
  • Proto-Oncogene Proteins
  • cdc25 Phosphatases / deficiency
  • cdc25 Phosphatases / genetics


  • Cell Cycle Proteins
  • Nuclear Proteins
  • Proto-Oncogene Proteins
  • Protein Kinases
  • Protein-Tyrosine Kinases
  • WEE1 protein, human
  • Protein-Serine-Threonine Kinases
  • polo-like kinase 1
  • CDC25B protein, human
  • cdc25 Phosphatases