Effects of bleomycin on growth kinetics and survival of Saccharomyces cerevisiae: a model of repair pathways.
In order to analyze the roles of some repair genes in the processing of bleomycin-induced DNA damage and, especially, the interrelationships among the involved repair pathways, we investigated the potentially lethal effect of bleomycin on radiosensitive mutants of Saccharomyces cerevisiae defective in recombination, excision, and RAD6-dependent DNA repair. Using single, double, and triple rad mutants, we analyzed growth kinetics and survival curves as a function of bleomycin concentration. Our results indicate that genes belonging to the three epistasis groups interact in the repair of bleomycin-induced DNA damage to different degrees depending on the concentration of bleomycin. The most important mechanisms involved are recombination and postreplication repair. The initial action of a potentially inducible excision repair gene could provide intermediate substrates for the RAD6- and RAD52-dependent repair processes. Interaction between RAD6 and RAD52 genes was epistatic for low bleomycin concentrations. RAD3 and RAD52 genes act independently in processing DNA damage induced by high concentrations of bleomycin. The synergistic interaction observed at high concentrations in the triple mutant rad2-6 rad6-1 rad52-1 indicates partial independence of the involved repair pathways, with possible common substrates. On the basis of the present results, we propose a heuristic model of bleomycin-induced DNA damage repair.
Keszenman
D J
DJ
Departamento de Biofísica, Facultad de Medicinia, Universidad de la República, Montevideo, Uruguay.
Salvo
V A
VA
Nunes
E
E
D001761:Bleomycin / Q000494:pharmacology* / Q000633:toxicity; D002455:Cell Division; D004249:DNA Damage / Q000502:physiology*; D004260:DNA Repair / Q000502:physiology*; D004261:DNA Replication / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004843:Epistasis, Genetic; D008954:Models, Biological; D009154:Mutation; D011836:Radiation Tolerance / Q000235:genetics; D011995:Recombination, Genetic; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000254:growth & development*
D001761:Bleomycin