Enhanced stimulation of chromosomal translocations by radiomimetic DNA damaging agents and camptothecin in Saccharomyces cerevisiae rad9 checkpoint mutants

Saccharomyces cerevisiae rad9 checkpoint mutants exhibit pleiotropic phenotypes, including higher frequencies of chromosome loss, radiation sensitivity, and decreased induction of DNA damage-inducible genes. We had previously shown that rad9 mutants exhibit higher frequencies of DNA damage-associated translocations but lower frequencies of DNA damage-associated sister chromatid exchange (SCE), compared to wild type. Herein, we have shown that differences between the frequencies of DNA damage-associated recombination in the rad9 mutant and wild type depend on the identity and the concentration of the DNA damaging agent. Translocation and SCE frequencies were measured in strains containing truncated his3 fragments, located either on chromosomes II and IV, or located in tandem on chromosome IV, respectively. DNA damage-associated frequencies of translocations after exposure to hydrogen peroxide (H2O2), bleomycin, phleomycin, cisplatin, and camptothecin are higher in the rad9 diploid than in wild type. However, translocation frequencies after exposure to 4-nitroquinoline 1-oxide (4-NQO) and N-methyl-N-nitro-N-nitrosoguanidine (MNNG) are similar in rad9 and wild-type strains. We suggest that the deficiency in triggering G(2) arrest after exposure to specific DNA damaging agents results in the higher levels of DNA damage-associated translocations in rad9 mutants. (C) 2004 Elsevier B.V. All rights reserved.