title: Inactivation of p53 results in high rates of homologous recombination.
abstract: Using a plasmid substrate which integrates into the genome, we determined that the rate of homologous recombination was suppressed by p53. Human tumor cell lines, mutant or null for p53 had recombination rates 10000-times greater than primary fibroblasts. When isogenic cell pairs from tumor cells or primary fibroblasts were compared, differing only 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 papilloma virus, or by genetic deletion led to the same result. Our results suggest that p53 suppresses spontaneous homologous recombination, and that 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 association are not yet established. It is suggested that suppression of homologous recombination is the means by which p53 maintains genetic stability.
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston 02114, USA.
authors.forename: K L
authors.initials: KL
authors.lastname: Mekeel
authors.forename: W
authors.initials: W
authors.lastname: Tang
authors.forename: L A
authors.initials: LA
authors.lastname: Kachnic
authors.forename: C M
authors.initials: CM
authors.lastname: Luo
authors.forename: J S
authors.initials: JS
authors.lastname: DeFrank
authors.forename: S N
authors.initials: SN
authors.lastname: Powell
mesh_terms: D015153:Blotting, Western; D002471:Cell Transformation, Neoplastic; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000235:genetics; D005347:Fibroblasts / Q000473:pathology / Q000502:physiology; D005434:Flow Cytometry; D006801:Humans; D009369:Neoplasms / Q000235:genetics; D010957:Plasmids / Q000235:genetics; D011995:Recombination, Genetic; D012680:Sensitivity and Specificity; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000502:physiology*
chemical_list: D004273:DNA, Neoplasm; D016159:Tumor Suppressor Protein p53