A widespread transposable element masks expression of a yeast copper transport gene.
The trace element copper (Cu) is essential for cell growth. In this report we describe the identification of a new component of the high-affinity 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 activity, ferrous iron transport, and respiratory proficiency to strains lacking the CTR1 (Cu transporter 1) gene. In most commonly used Saccharomyces cerevisiae laboratory strains, expression of CTR3 is abolished by a Ty2 transposon insertion that separates the CTR3 promoter from the transcriptional start sites by 6 kb. In strains that do not possess a Ty2 transposon at the CTR3 locus, expression of CTR3 is repressed by copper 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 copper transport, the expression of both proteins provides maximal copper uptake and growth rate under copper-limiting conditions. These results underscore the importance of mobile DNA elements in the alteration of gene function and phenotypic variation.
Knight
S A
SA
Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor 48109-0606, USA.
Labbé
S
S
Kwon
L F
LF
Kosman
D J
DJ
Thiele
D J
DJ
D000595:Amino Acid Sequence; D017920:Antiporters / Q000096:biosynthesis* / Q000235:genetics / Q000302:isolation & purification; D001483:Base Sequence; D001692:Biological Transport; D027682:Cation Transport Proteins; D002455:Cell Division; D002462:Cell Membrane / Q000737:chemistry; D003300:Copper / Q000378:metabolism*; D000079923:Copper Transporter 1; D004251:DNA Transposable Elements; D005656:Fungal Proteins / Q000096:biosynthesis / Q000235:genetics*; D015966:Gene Expression Regulation, Fungal; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D010084:Oxidation-Reduction; D011401:Promoter Regions, Genetic; D000080083:SLC31 Proteins; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D017386:Sequence Homology, Amino Acid; D013347:Subcellular Fractions
D017920:Antiporters; C490078:CTR1 protein, S cerevisiae; C100982:CTR3 protein, S cerevisiae; D027682:Cation Transport Proteins; D000079923:Copper Transporter 1; D004251:DNA Transposable Elements; D005656:Fungal Proteins; D008565:Membrane Proteins; D000080083:SLC31 Proteins; D029701:Saccharomyces cerevisiae Proteins; D003300:Copper