title: p53 prevents immature escaping from cell cycle G2 checkpoint arrest through inhibiting cdk2-dependent NF-Y phosphorylation.
abstract: OBJECTIVE
  Recent studies have suggested that p53 regulates the G2 checkpoint in the cell cycle and this function is required for the maintenance of genomic integrity. In this study, we addressed a role of p53 in escaping from cell cycle G2 arrest following DNA damage.
  
  
  METHODS
  Cell cycle checkpoint arrest in the human colon cancer cell line HCT116 and its derivatives carry p53 or p21 deletions, were examined by FACS analysis, immunoprecipitation, Western blot and IP-kinase assay.
  
  
  RESULTS
  While the cells with functional p53 were arrested at both the G1 and G2 checkpoints, the p53-deficient cells failed to arrest at G1, but they were arrested at G2. However, the p53-deficient cells failed to sustain G2 checkpoint arrest and they entered mitosis earlier than did the p53-positive cells and so this resulted in extensive cell death. Cdc2 kinase becomes reactivated in p53-deficient cells in association with entry into mitosis, but not in the p53-positive cells. Upon DNA damage, the p21-deficient cells, like the p53-negative cells, not only failed to repress cdk2-dependent NF-Y phosphorylation, but they also failed to repress the expression of such cell cycle G2-regulatory genes as cdc2, cyclin B, RNR-R2 and cdc25C, which have all been previously reported as targets of NF-Y transcription factor.
  
  
  CONCLUSIONS
  p53 is essential to prevent immature escaping from cell cycle G2 checkpoint arrest through p21-mediated cdk2 inactivation, and this leads to inhibition of cdk2-dependent NF-Y phosphorylation and NF-Y dependent transcription of the cell cycle G2-regulatory genes, including cdc2 and cyclin B.
authors.affiliation: National Research Laboratory of Cell Cycle Regulation, Department of Microbiology, Dankook University College of Medicine, Cheonan, Korea.
authors.forename: Un-Jung
authors.initials: UJ
authors.lastname: Yun
authors.forename: Heui-Dong
authors.initials: HD
authors.lastname: Park
authors.forename: Deug Y
authors.initials: DY
authors.lastname: Shin