The oxidative stress response in the yeast Saccharomyces cerevisiae and its control by YAP1 and SKN7

The cellular response to H2O2 in the yeast Saccharomyces cerevisiae was analyzed by the comparative two dimensional (2D) gel electrophoresis. Protein synthesis rates were measured by pulse labeling under H2O2 stress. H2O2-responsive targets include ROI scavenging activities and a number of heat shock proteins. Oxidative stress also results in a stimulation of protein degradation pathway and a slowdown of protein biosynthetic processes. The enzymes of carbohydrate metabolism are modulated by oxidative stress, so that carbohydrate fluxes are directed to the generation of NADPH. Therefore, H2O2 stress induces global response in which many cellular processes are directed to increase defense activities.; The regulatory roles of YAP1 and SKN7 in the H2O2 stress response were analyzed using Northern blotting and 2D gel approach. Thirty-six of the H2O2-inducible genes are controlled by YAP1 and ten of these YAP1 targets also requires SKN7 for their induction by H2O2. Therefore, YAP1 and SKN7 cooperate for the induction of a subset of H2O2 stimulon, although the function of YAP1 can be independent on SKN7. This result demonstrates that the yeast antioxidant defenses are organized into at least two separate but overlapping regulons.; As one of the approaches to study specificity of oxidative stress responses, diamide-induced stress response was analyzed and compared to that of H 2O2. Diamide stress response is also mediated by YAP1 and SKN7 with the similar mode to H2O2 stress response, but a few aspects of antioxidant gene regulation are different between the diamide and H2O2 stress responses. YAP1 appears to be activated differently to discriminate the stresses imposed by diamide and H2O2.; SHR1 was isolated by the selection of the activity which can complement skn7 strain hypersensitivity to tBOOH. SHR1 is a novel antioxidant which probably has peroxidase activity. Overexpression or null mutation of SHR1 demonstrates that SHR1 protein is important for the tolerance against tBOOH, diamide and cadmium but not H 2O2 and menadion. SHR1 is induced by several oxidants and the induction is regulated by both YAP1 and SKN7.