Role of thioredoxin reductase in the Yap1p-dependent response to oxidativestress in Saccharomyces cerevisiae

The Saccharomyces cerevisiae Yap1p transcription factor is required for the H2O2-dependent activation of many antioxidant genes including the TRX2 gen e encoding thioredoxin 2. To identify factors that regulate Yap1p activity, we carried out a genetic screen for mutants that show elevated expression of a TRX2-HIS3 fusion in the absence of H2O2. Two independent mutants isola ted in this screen carried mutations in the TRR1 gene encoding thioredoxin reductase. Northern blot and whole-genome expression analysis revealed that the basal expression of most Yap1p targets and many other H2O2-inducible g enes is elevated in Delta trr1 mutants in the absence of external stress. I n Delta trr1 mutants treated with H2O2, the Yap1p targets, as well as genes comprising a general environmental stress response and genes encoding prot ein-folding chaperones, are hyperinduced. However, despite the elevated exp ression of genes encoding antioxidant enzymes, Delta trr1 mutants are extre mely sensitive to H2O2. The results suggest that cells lacking thioredoxin reductase have diminished capacity to detoxify oxidants and/or to repair ox idative stress-induced damage and that the thioredoxin system is involved i n the redox regulation of Yap1p transcriptional activity.