A new link in the chain of events that cause cells with damaged DNA to pause in the cell cycle until the DNA is repaired or to undergo apoptosis is described by Hirao et al. This DNA damage-induced checkpoint requires activation of the transcription factor p53. The authors' analysis of checkpoint function in mouse cells lacking the protein kinase Chk2 indicates that Chk2 is required for stabilization of p53 in response to DNA damage. They also show that Chk2 can directly phosphorylate p53. Failure of this checkpoint pathway may result in cancer if cells harboring damaged DNA are allowed to replicate without first repairing their DNA. The accompanying Perspective by Carr discusses in greater detail the molecular aspects of checkpoint control and cell-cycle arrest.
Hirao, A., Kong, Y.-Y., Matsuoka, S., Wakeham, A., Ruland, J., Yoshida, H., Liu, D., Elledge, S.J., and Mak, T.W. (2000) DNA damage-induced activation of p53 by the checkpoint kinase Chk2. Science 287: 1824-1827. [Abstract] [Full Text]