A WIDESPREAD TRANSPOSABLE ELEMENT MASKS EXPRESSION OF A YEAST COPPER TRANSPORT GENE

The trace element copper (Cu) is essential for cell growth. In this re port we describe the identification of a new component of the high-aff inity Cu transport machinery in yeast, encoded by the CTR3 gene. Ctr3p is a small intracellular cysteine-rich integral membrane protein that restores high-affinity Cu uptake, Cu, Zn superoxide dismutase activit y, ferrous iron transport, and respiratory proficiency to strains lack ing the CTR1 (Cu transporter 1) gene. In most commonly used Saccharomy ces cerevisiae laboratory strains, expression of CTR3 is abolished by a Ty2 transposon insertion that separates the CTR3 promoter from the t ranscriptional start sites by 6 kb. In strains that do not possess a T y2 transposon at the CTR3 locus, expression of CTR3 is repressed by co pper and activated by copper starvation. In such strains inactivation of both CTR1 and CTR3 is required to generate lethal copper-deficient phenotypes. Although Ctr1p and Ctr3p can function independently in cop per transport, the expression of both proteins provides maximal copper uptake and growth rate under copper-limiting conditions. These result s underscore the importance of mobile DNA elements in the alteration o f gene function and phenotypic variation.