After DNA damage, many cells appear to enter a sustained arrest in the
G(2) 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 tra
nscriptionally activating the cyclin-dependent kinase inhibitor p21. A
fter disruption of either the p53 or the p21 gene, gamma radiated cell
s progressed into mitosis and exhibited a G(2) DNA content only becaus
e of a failure of cytokinesis. Thus, p53 and p21 appear to be essentia
l for maintaining the G(2) checkpoint in human cells.