Arsenic is a toxic
metalloid that affects human health by causing numerous diseases and by being used in the treatment of
acute promyelocytic leukemia. Saccharomyces cerevisiae (budding yeast) has been extensively utilized to elucidate the molecular mechanisms underlying
arsenic toxicity and resistance in eukaryotes. In this study, we applied a genomic
DNA overexpression strategy to identify yeast genes that provide
arsenic resistance in wild-type and
arsenic-sensitive S. cerevisiae cells. In addition to known
arsenic-related genes, our genetic screen revealed novel genes, including PHO86, VBA3, UGP1, and TUL1, whose overexpression conferred resistance. To gain insights into possible resistance mechanisms, we addressed the contribution of these genes to cell growth, intracellular
arsenic, and
protein aggregation during
arsenate exposure. Overexpression of PHO86 resulted in higher cellular
arsenic levels but no additional effect on
protein aggregation, indicating that these cells efficiently protect their intracellular environment. VBA3 overexpression caused resistance despite higher intracellular
arsenic and
protein aggregation levels. Overexpression of UGP1 led to lower intracellular
arsenic and
protein aggregation levels while TUL1 overexpression had no impact on intracellular
arsenic or
protein aggregation levels. Thus, the identified genes appear to confer
arsenic resistance through distinct mechanisms but the molecular details remain to be elucidated.