Genetic Determinants for Yeast's Resistance to Copper, Iron and Zinc Overload

Abstract

The metals iron, copper and zinc, although essential for life, are toxic when present in excess. We have conducted a parallel analysis of yeast deletion mutants under metal overload conditions to simultaneously evaluate the growth phenotype of more than 4700 strains. We established the genetic requirements of the yeast Saccharomyces cerevisiae when grown in the presence of toxic concentrations of iron sulfate, copper sulfate and zinc chloride. These screens identified distinct but overlapping mutant sensitivity profiles. In general, genes encoding proteins involved in intracellular membrane trafficking and vacuole morphogenesis were essential in all three conditions. Highly essential genes included SUR1 and CSG2 in iron, SXM1 in copper and ZRC1 and DAP1 in zinc. YDR186C and YHR045W, encoding putative proteins of unknown function, were identified as potentially novel genes for yeast resistance to zinc overload. Our data suggest that any of these metals, when present in excess, induce secondary metal deficiency, strengthening the connection between iron, copper and zinc metabolism in yeast. In conclusion, our results indicated the requirement of highly‐conserved biological processes in response to iron, copper and zinc toxicity, and identified potentially novel genes that may play a role in metal homeostasis and/or detoxification in yeast. Funded by NIEHS Superfund Basic Research Program [P42 ES004705‐19] and the UC Berkeley Faculty on Research Grant