INCREASE OF SPONTANEOUS INTRACHROMOSOMAL HOMOLOGOUS RECOMBINATION IN MAMMALIAN-CELLS EXPRESSING A MUTANT P53 PROTEIN

Homologous recombination plays an essential role in processes involved in genome stability/instability, such as molecular evolution, gene di versification, meiotic chromosome segregation, DNA repair and chromoso mal rearrangements, p53 devoid cells exhibit predisposition to neoplas ia, defects in G(1) checkpoint and high genetic instability but a norm al rate of point mutations, We investigated the effect of a p53 mutati on, on spontaneous homologous recombination between intrachromosomal d irect repeat sequences, in mouse L cells. In these cells, wild type fo r the p53 gene, we have overexpressed the mutant p53(175)(Arg>His) pro tein leading to a p53 mutant phenotype, as verified by the absence of a G(1) arrest after gamma-irradiation. We show that the rate of sponta neous recombination is increased from five- to 20-fold in the mutant p 53 lines, Moreover, this increase is observed in gene conversion as we ll as in deletion events, Our results provide new insights into the mo lecular mechanisms of genetic instability due to a defect of p53.