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Loss of a p53-associated G1 Checkpoint Does Not Decrease Cell Survival following DNA Damage¹

Departments of Oncology [W. J. S., W. G. N., M. B. K.] and Pathology [R. J. S.], Johns Hopkins University School of Medicine, Baltimore, Maryland 21287

Cell cycle checkpoints regulate progression through the cell cycle. In yeast, loss of the G₂ checkpoint by mutation of the rad9 gene results in increased genetic instability as well as increased sensitivity to ionizing radiation. In contrast, comparing clonogenic survival of cells which are isogeneic except for p53 functional status, we find that loss of a G₁ check-point in mammalian cells is not associated with increased sensitivity to the lethal effects of ionizing radiation or a topoisomerase I inhibitor, camptothecin. These results indicate that increased sensitivity to DNA-damaging agents is not necessarily a defining feature of a mammalian cell cycle checkpoint. Furthermore, in light of a recent link of p53 function to radiation-induced apoptosis in hematopoietic cells, these observations suggest that p53-dependent apoptosis is a cell type-specific phenomenon and thus predict that the biological consequences of loss of p53 function will be cell type specific.

¹ This work was supported by Grant ES05777 from the NIH, Grants 3187 and 3223 from The Council for Tobacco Research, and the Dutch Cancer Society.

² To whom requests for reprints should be addressed.

Received 6/29/93. Accepted 8/ 3/93.

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