Increase of spontaneous intrachromosomal homologous recombination in mammalian cells expressing a mutant p53 protein

• Published in: Oncogene Vol. 14; no. 9; pp. 1117 - 1122
• Main Authors: BERTRAND, P, ROUILLARD, D, BOULET, A, LEVALOIS, C, SOUSSI, T, LOPEZ, B. S
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing 06-03-1997; Nature Publishing Group
• Subjects: Animals; Biological and medical sciences; Cell Line; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Chromosome rearrangements; Cloning, Molecular; DNA repair; Fundamental and applied biological sciences. Psychology; Gamma Rays; Gene conversion; Gene Conversion - genetics; Gene Deletion; Genomes; Genomic instability; Homologous recombination; L cells; Mammalia; Mammalian cells; Meiosis; Mice; Molecular and cellular biology; Molecular evolution; Molecular modelling; Mutants; Mutation; p53 Protein; Phenotypes; Recombination, Genetic - genetics; Tumor Suppressor Protein p53 - genetics; γ Radiation; Repeated sequence; Homologous recombination; Rodentia; Biological activity; Protein p53; Vertebrata; Mammalia; Cell line; Mouse; Instability; Mutation; Genome; Tumor suppressor gene
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/sj.onc.1200931

Homologous recombination plays an essential role in processes involved in genome stability/instability, such as molecular evolution, gene diversification, meiotic chromosome segregation, DNA repair and chromosomal rearrangements. p53 devoid cells exhibit predisposition to neoplasia, defects in G1 checkpoint and high genetic instability but a normal rate of point mutations. We investigated the effect of a p53 mutation, on spontaneous homologous recombination between intrachromosomal direct repeat sequences, in mouse L cells. In these cells, wild type for the p53 gene, we have overexpressed the mutant p53(175(Arg>His)) protein leading to a p53 mutant phenotype, as verified by the absence of a G1 arrest after gamma-irradiation. We show that the rate of spontaneous recombination is increased from five- to 20-fold in the mutant p53 lines. Moreover, this increase is observed in gene conversion as well as in deletion events. Our results provide new insights into the molecular mechanisms of genetic instability due to a defect of p53.