A functional copperthionein (CUP1) gene in Saccharomyces cerevisiae is essential to prevent copper-mediated cytotoxicity, but is dispensable for cell growth in the absence of exogenous copper. The CUP1 gene is negatively autoregulated, as observed by the necessity for a functional CUP1 gene in order to repress basal level transcription from the CUP1 promoter. Both the copper protection and transcriptional autoregulatory functions can be complemented by expression in yeast of either of two monkey metallothionein isoform cDNAs. The expression of the CUP1 gene is induced at the level of transcription by copper via cis-dominant upstream control sequences which are tandemly repeated. Synthetic CUP1 upstream control sequences confer copper inducibility on a heterologous yeast promoter in a manner similar to that observed for the authentic upstream control region.