p53 directly enhances rejoining of DNA double-strand breaks with cohesive ends in gamma-irradiated mouse fibroblasts

The p53 gene regulates the cell cycle response to DNA damage, which may all ow time for adequate DNA repair, We asked whether p53 could directly increa se the repair of defined double-strand breaks (DSBs) by nonhomologous end-j oining in gamma-irradiated mouse embryonic fibroblasts with differing p53 s tatus. By using an episomal plasmid reactivation assay; we found that prese nce of wild-type p53 enhanced rejoining of DSBs with short complementary en ds of single-stranded DNA. p53 appeared to be directly involved in this reg ulation, because rejoining enhancement was dependent on the presence of non specific DNA binding activity as mediated by the COOH-terminal domain and w as independent of transactivating function. We hypothesize that tumor cells lacking p53 and normal cells with nad-type p53 may use different pathways for repair of radiation-induced DSBs.