Cell cycle re-entry mechanisms after DNA damage checkpoints: giving it some gas to shut off the breaks!
In order to maintain genetic integrity, cells are equipped with cell cycle checkpoints that detect DNA damage, orchestrate repair, and if necessary, eliminate severely damaged cells by inducing apoptotic cell death. The mitotic machinery is now emerging as an important determinant of the cellular responses to DNA damage where it functions as both the downstream target and the upstream regulator of the G2/M checkpoint. Cell cycle kinases and the DNA damage checkpoint kinases appear to reciprocally control each other. Specifically, cell cycle kinases control the inactivation of DNA damage checkpoint signaling. Termination of a DNA damage response by mitotic kinases appears to be an evolutionary conserved mechanism that allows resumption of cell cycle progression. Here we review recent reports in which molecular mechanisms underlying checkpoint silencing at the G2/M transition are elucidated.
van Vugt
Marcel A T M
MA
Department of Medical Oncology, University Medical Centre Groningen, Groningen, The Netherlands. m.vugt@onco.umcg.nl
Yaffe
Michael B
MB
D018797:Cell Cycle Proteins / Q000378:metabolism; D002455:Cell Division; D064447:Checkpoint Kinase 2; D004249:DNA Damage; D004260:DNA Repair; D016195:G2 Phase; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008938:Mitosis; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D000071857:Tumor Suppressor p53-Binding Protein 1; D000097869:Polo-Like Kinase 1
D018797:Cell Cycle Proteins; D064447:Checkpoint Kinase 2; D047908:Intracellular Signaling Peptides and Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D000071857:Tumor Suppressor p53-Binding Protein 1; D000097869:Polo-Like Kinase 1; C498301:TP53BP1 protein, human; C578634:CHEK2 protein, human