Increased DNA double strand breakage is responsible for sensitivity of the pso3-1mutant of Saccharomyces cerevisiaeto hydrogen peroxide

Escherichia coliendonuclease III (endo III) is the key repair enzyme essential for removal of oxidized pyrimidines and abasic sites. Although two homologues of endo III, Ntg1 and Ntg2, were found in Saccharomyces cerevisiae, they do not significantly contribute to repair of oxidative DNA damage in vivo. This suggests that an additional activity(ies) or a regulatory pathway(s) involved in cellular response to oxidative DNA damage may exist in yeast. The pso3-1mutant of S. cerevisiaewas previously shown to be specifically sensitive to toxic effects of hydrogen peroxide (H2O2) and paraquat. Here, we show that increased DNA double strand breakage is very likely the basis of sensitivity of the pso3-1mutant cells to H2O2. Our results, thus, indicate an involvement of the Pso3 protein in protection of yeast cells from oxidative stress presumably through its ability to prevent DNA double strand breakage. Furthermore, complementation of the repair defects of the pso3-1mutant cells by E. coliendo III has been examined. It has been found that expression of the nthgene in the pso3-1mutant cells recovers survival, decreases mutability and protects yeast genomic DNA from breakage following H2O2treatment. This might suggest some degree of functional similarity between Pso3 and Nth.