Polo-like kinase-1 controls recovery from a G2 DNA damage-induced arrest in mammalian cells.
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.
van Vugt
Marcel A T M
MA
Division of Molecular Biology, H8, Netherlands Cancer Institute, Plesmanlaan 121, 1066CX Amsterdam, The Netherlands.
Brás
Alexandra
A
Medema
René H
RH
D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D004249:DNA Damage / Q000235:genetics*; D016195:G2 Phase / Q000235:genetics / Q000502:physiology*; D018816:Genes, cdc / Q000502:physiology*; D006801:Humans; D008938:Mitosis / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D020687:cdc25 Phosphatases / Q000172:deficiency / Q000235:genetics; D000097869:Polo-Like Kinase 1
D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins; D020687:cdc25 Phosphatases; D000097869:Polo-Like Kinase 1; C499349:WEE1 protein, human; C517008:CDC25B protein, human