Hydrogen peroxide causes RAD9-dependent cell cycle arrest in G2 in Saccharomyces cerevisiae whereas menadione causes G1 arrest independent of RAD function

This study shows differences at the level of cell cycle arrest between the response of yeast cells to hydrogen peroxide and superoxide stress. These include both cell cycle phases at which arrest occurs and the involvement of the RADS checkpoint gene. Wild-type and rads cells were treated with hydrogen peroxide or the superoxide-generating agent menadione, rad9 mutants were up to 100-fold more sensitive to hydrogen peroxide but not affected in their resistance to menadione, Hydrogen peroxide caused G(2)-phase arrest, whereas menadione treated cells arrested in G(1) . G(2) arrest, induced by methyl 2-benzimidazil carbamate, increased cellular resistance to hydrogen peroxide but not to menadione. G(1) arrest mediated by alpha-factor caused an increase in survival of wild-type cells treated with menadione but not with hydrogen peroxide. A cdc28 mutant arrested in G(1) was significantly more sensitive to hydrogen peroxide than other cde mutants arrested in later phases, including G(2). rad9 cells have normal stationary phase resistance to hydrogen peroxide, the ability to adapt to it, glutathione content and induction of genes via the stress responsive element. Although rad9-dependent G(2) arrest is important, other rad9-dependent factors may be involved in the resistance of cells to hydrogen peroxide since arrest in G(2) did not make rad9 cells fully resistant.