Identification of genes affecting selenite toxicity and resistance in Saccharomyces cerevisiae

Recent studies associating dietary selenium with reduced cancer susceptibil ity have aroused interest in this substance. In the millimolar range, selen ite is toxic and slightly mutagenic for yeast. We show that selenite-treate d yeast cells tend to arrest as large budded cells and that this arrest is abolished in a rad9 mutant that is significantly sensitive to selenite. Int erestingly, a rev3 mutant affected in the error-prone repair pathway is als o sensitive to selenite, whereas mutations in the other DNA repair pathways do not strongly affect resistance to selenite. We propose that selenite tr eatment leads to DNA damage inducing the RAD9-dependent cell cycle arrest. Selenite-induced DNA damage could be converted to mutations by the Rev3p-de pendent lesion bypass system, thus allowing the cell cycle to progress. We have also investigated the selenite detoxification mechanisms and identifie d three genes involved in this process. In the present study, we show that lack of the cadmium glutathione-conjugate vacuolar pump Ycf1p or overexpres sion of the sulphite resistance membrane protein Ssu1p enhance the capacity of yeast cells to resist selenite treatment. Finally, we show that overexp ression of the glutathione reductase Glr1p increases resistance to selenite , suggesting that selenite toxicity in yeast is closely linked to its oxida tive capacity.