INACTIVATION OF P53 RESULTS IN HIGH-RATES OF HOMOLOGOUS RECOMBINATION

Using a plasmid substrate which integrates into the genome, we determi ned that the rate of homologous recombination was suppressed by p53, H uman tumor cell lines, mutant or null for p53 had recombination rates 10 000-times greater than primary fibroblasts. When isogenic cell pair s from tumor cells or primary fibroblasts were compared, differing onl y in one genetic change which inactivated p53, the recombination rate increased >100-fold. Functional inactivation of p53 by dominant mutant p53, by large T antigen of SV40 virus, by E6 protein of human papillo ma virus, or by genetic deletion led to the same result. Our results s uggest that p53 suppresses spontaneous homologous recombination, and t hat p53 is not required for recombination to proceed, The mechanism of recombination suppression may be related to the reported association of p53 with Rad 51, but the functional consequences of this associatio n are not yet established. It is suggested that suppression of homolog ous recombination is the means by which p53 maintains genetic stabilit y.