P53 DEFICIENCY DOES NOT AFFECT THE ACCUMULATION OF POINT MUTATIONS INA TRANSGENE TARGET

DNA repair is required by organisms to prevent the accumulation of mut ations and to maintain the integrity of genetic information. Mammalian cells that have been treated with agents that damage DNA have an incr ease in p53 levels, a p53-dependent arrest at G(1) in the cell cycle, and a p53-dependent apoptotic response. It has been hypothesized that this block in cell cycle progression is necessary to allow time for DN A repair or to direct the damaged cell to an apoptotic pathway. This h ypothesis predicts that p53-deficient cells would have an abnormal apo ptotic response and exhibit a ''mutator'' phenotype. Using a sensitive assay for the accumulation of point mutations, small deletions, and i nsertions, we have directly tested whether p53-deficient cells exhibit an increased frequency of mutation before and after exposure to DNA-d amaging agents. We report that wild-type and p53-deficient fibroblasts , thymocytes, and tumor tissue have indistinguishable rates of point m utation accumulation in a transgenic lacI target gene. These results s uggest that the role of p53 in G(1) checkpoint control and tumor suppr ession does not affect the accumulation of point mutations.