Requirement for p53 and p21 to Sustain G <sub>2</sub> Arrest After DNA Damage
Fred Bunz(Johns Hopkins University), Annie Dutriaux(Johns Hopkins University), Christoph Lengauer(Johns Hopkins University), Todd Waldman(Johns Hopkins University), Steven Zhou(Johns Hopkins University), Jeremy Brown(Johns Hopkins University), John M. Sedivy(Johns Hopkins University), Kenneth W. Kinzler(Johns Hopkins University), Bert Vogelstein(Johns Hopkins University)
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Abstract
After DNA damage, many cells appear to enter a sustained arrest in the G2 phase of the cell cycle. It is shown here that this arrest could be sustained only when p53 was present in the cell and capable of transcriptionally activating the cyclin-dependent kinase inhibitor p21. After disruption of either the p53 or the p21 gene, gamma radiated cells progressed into mitosis and exhibited a G2 DNA content only because of a failure of cytokinesis. Thus, p53 and p21 appear to be essential for maintaining the G2 checkpoint in human cells.
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