Mutagenesis induced by mono- and bi-functional alkylating agents in yeast mutants sensitive to photo-addition of furocoumarins (pso)

Abstract

The inactivation and the induction of forward and reverse mutations by a mono- and a bifunctional nitrogen mustard in 3 pso mutants of Saccharomyces cerevisiae, initially selected for their sensitivity to psoralen photo-addition, were compared with that of the wild-type. The pso1-1 mutant was very sensitive to both alkylating agents, and the mutagenicity was abolished. This correlates with the defect in the error-prone repair capacity for lesions induced by psoralen photo-addition and radiations already observed for this mutant. Therefore it appears that the PSO1+ gene product acts on a spectrum of DNA lesions. The pso2-1 mutant was highly sensitive to the lethal effect of the bifunctional nitrogen mustard and was only slightly sensitive to the monofunctional one. For both agents a reduction in induced mutagenesis was seen. The same was true for mono- and bifunctional psoralen derivatives. The pso2-1 mutant having the same sensitivity as the wild-type to UV and ionizing radiations, it is suggested that the PSO2+ gene product is predominantly necessary for the repair of cross-links irrespective of their molecular nature. In contrast with psoralen photo-induced inactivation the pso3-1 mutant had the same sensitivity as the wild-type to alkylating agents. However, a reduction in induced mutagenesis was seen in both cases. This response was modulated according to dose and type of mutation. Consequently, it appeared that the PSO3+ gene product acts specifically on psoralen photo-induced sub-lethal lesions and on a fraction of premutagenic lesions independently of their structure.