The requirement for yeast superoxide dismutase is bypassed through mutations in BSD2, a novel metal homeostasis gene.
Oxygen toxicity in Saccharomyces cerevisiae strains lacking superoxide dismutase can be suppressed through mutations in either the BSD1 or BSD2 gene. In this report, we demonstrate that the BSD2 gene normally functions in the homeostasis of heavy metal ions. A mutation in BSD2 not only reverses the aerobic defects of yeast strains lacking superoxide dismutase but also is associated with an increased sensitivity to copper and cadmium toxicity and an elevation in copper ion accumulation. The BSD2 gene was cloned by functional complementation and is predicted to encode a novel 37.5-kDa protein with three potential transmembrane domains. The mutant bsd2-1 allele was isolated and found to contain a single C-to-T transition changing a centrally located proline to a serine. This substitution results in total inactivation of BSD2, since the bsd2-1 mutation is identical to a bsd2 delta gene deletion in phenotype. BSD2 is expressed in yeast cells as a 1.5-kb mRNA. Although the gene functions in copper detoxification, BSD2 is not induced by copper ions, as is the case with S. cerevisiae metallothioneins. A probable role for copper ions in the bsd2 reversal of oxidative damage is discussed.
Liu
X F
XF
Department of Environmental Health Sciences, Johns Hopkins University School of Hygiene and Public Health, Baltimore, MD 21205.
Culotta
V C
VC
D000483:Alleles; D000595:Amino Acid Sequence; D001483:Base Sequence; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D003300:Copper / Q000378:metabolism; D004271:DNA, Fungal / Q000235:genetics; D005609:Free Radicals; D017353:Gene Deletion; D005800:Genes, Fungal; D006706:Homeostasis / Q000235:genetics; D008670:Metals / Q000378:metabolism* / Q000494:pharmacology; D008969:Molecular Sequence Data; D009154:Mutation; D017382:Reactive Oxygen Species / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*
D004271:DNA, Fungal; D005609:Free Radicals; D008670:Metals; D017382:Reactive Oxygen Species; D003300:Copper; D013482:Superoxide Dismutase