Repression of sulfate assimilation is an adaptive response of yeast to the oxidative stress of zinc deficiency

Abstract

The Zap1 transcription factor is a central player in the response of yeast to changes in zinc status. Previous studies identified over 80 genes activated by Zap1 in zinc-limited cells. In this report, we identified 36 genes repressed in a zinc- and Zap1-responsive manner. As a result, we have identified a new mechanism of Zap1-mediated gene repression whereby transcription of theMET3,MET14, andMET16genes is repressed in zinc-limited cells. These genes encode the first three enzymes of the sulfate assimilation pathway.Wefound that MET30, encoding a component of the SCFMet30 ubiquitin ligase, is a direct Zap1 target gene.MET30expression is increased in zinc-limited cells, and this leads to degradation of Met4, a transcription factor responsible for MET3, MET14, and MET16 expression. Thus, Zap1 is responsible for a decrease in sulfate assimilation in zinc-limited cells. We further show that cells that are unable to down-regulate sulfate assimilation under zinc deficiency experience increased oxidative stress. This increased oxidative stress is associated with an increase in the NADP+/ NADPH ratio and may result from a decrease in NADPH-dependent antioxidant activities. These studies have led to new insights into how cells adapt to nutrient-limiting growth conditions. © 2009 by The American Society for Biochemistry and Molecular Biology, Inc.