title: CRS5 encodes a metallothionein-like protein in Saccharomyces cerevisiae.
abstract: Protection from copper toxicity in the bakers' yeast Saccharomyces cerevisiae involves the action of a copper binding metallothionein encoded by the CUP1 locus. To identify additional factors contributing to copper ion homeostasis and detoxification, we screened a genomic library for genes that confer high levels of copper resistance to yeast strains lacking CUP1. This screen led to the identification of the CRS5 (copper-resistant suppressor) gene. By sequence analyses, CRS5 encodes a small molecular weight cysteine-rich protein with an amino acid sequence bearing all the features of a eukaryotic metallothionein. The CRS5 polypeptide exhibits a striking similarity to a number of mammalian and invertebrate metallothioneins, yet shares surprisingly little homology with CUP1. In yeast, CRS5 is expressed as a 0.5-kilobase mRNA that is regulated both by copper ions and by oxidative stress, and expression is dependent upon ACE1, a copper and DNA binding transcription factor also known to regulate CUP1. Deletion of the chromosomal CRS5 locus was found to increase cellular sensitivity to copper, but not cadmium, toxicity. These studies support an important role for the CRS5 metallothionein-like protein in copper homeostasis and detoxification.
authors.affiliation: Department of Environmental Health Sciences, Johns Hopkins University School of Hygiene and Public Health, Baltimore, Maryland 21205.
authors.forename: V C
authors.initials: VC
authors.lastname: Culotta
authors.forename: W R
authors.initials: WR
authors.lastname: Howard
authors.forename: X F
authors.initials: XF
authors.lastname: Liu
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002352:Carrier Proteins; D003300:Copper / Q000378:metabolism* / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004352:Drug Resistance, Microbial; D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal / Q000235:genetics*; D006706:Homeostasis; D008668:Metallothionein / Q000235:genetics*; D008969:Molecular Sequence Data; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D013489:Suppression, Genetic; D014157:Transcription Factors / Q000378:metabolism; D014170:Transformation, Genetic
chemical_list: C089939:CRS5 protein, S cerevisiae; C500769:CUP1-1 protein, S cerevisiae; C060256:CUP2 protein, S cerevisiae; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C007121:copper thionein; D003300:Copper; D008668:Metallothionein