Abstract
The CUP1 locus in yeast confers resistance to copper toxicity. We determined the molecular basis for copper resistance in three yeast strains, with differing degrees of resistance. Increased resistance to copper is associated with overproduction of a low molecular weight copper-binding protein, copper-chelatin. Increased chelatin synthesis results from amplification of the CUP1r gene and increased synthesis of the copper inducible mRNA. The copper resistance level of a given strain correlates directly with the gene copy number.
Strains containing one copy and ten tandemly iterated copies of the CUP1 gene were studied. From the latter, a haploid strain with enhanced resistance was isolated following several selection cycles at elevated copper concentrations. This strain was disomic for chromosome VIII, the chromosome containing the CUP1 locus. The disomic chromosomes exhibit differential CUP1 gene amplification: 11 and 14 tandemly organized repeat units are found in the respective chromosome VIII homologues. We propose that the molecular mechanisms of gene amplification involve unequal sister chromatid exchange and intrachromosomal gene conversion, as well as disomy.
Similar content being viewed by others
References
Anderson RP, Roth JR (1977) Annu Rev Microbiol 31:473–505
Beach LR, Palmiter RD (1981) Proc Natl Acad Sci USA 78:2110–2114
Brenes-Pomales A, Lindegren G, Lindegren CC (1955) Nature 176:841–842
Davis RW, Botstein D, Roth JR (1980) Cold Spring Harbor Laboratory, Cold Spring Harbor, NY
Fogel S, Mortimer RK (1969) Proc Natl Acad Sci USA 62:96–100
Fogel S, Mortimer RK (1970) Mol Gen Genet 109:177–185
Fogel S, Welch JW (1982) Proc Natl Acad Sci USA 79:5342–5346
Fogel S, Mortimer RK, Lusnak K (1981) Mechanism of meiotic gene conversion, or wanderings on a foreign strand. In: Strathern JN, Jones EW, Broach JR (eds) The Molecular Biology of the Yeast Saccharomyces. Cold Spring Harbor Laboratory, pp 289–339
Fogel S, Choi T, Kilgore D, Lusnak K, Williamson M (1982) Recent Adv Yeast Mol Biol 1:269–288
Gall JC (1978) Harvey Lect 71:55–70
Hawthorne DC, Mortimer RK (1960) Genetics 45:1085–1110
Hurst DD, Fogel S, Mortimer RK (1972) Proc Natl Acad Sci USA 69:101–105
Jackson J, Fink GR (1981) Nature 292:306–311
Klein HL, Petes TD (1981) Nature 289:144–148
Kagi JHR, Nordberg M (1979) Metallothionein Birkhauser, Basel
Karin M, Richards R (1982) Nucleic Acids Res 10:3165–3173
Mortimer RK, Fogel S (1974) Genetical interference and gene conversion. In: Grell G (ed) Mechanisms in Recombination. Plenum Press, New York, pp 236–248
Petes TD (1980) Cell 19:765–774
Premakumar R, Winge RD, Wiley DR, Rajagopalan KV (1975) Arch Biochem Biophys 170:278–288
Prinz R, Weser U (1975) Hoppe Seylers Z Physiol Chem 356:767–776
Rigby PW, Dieckmann M, Rhodes C, Berg P (1977) J Mol Biol 113:237–251
Schimke RT (1982) In: Gene Amplification. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, pp 317–333
Spradling AC, Mahowald AP (1980) Proc Natl Acad Sci USA 77:1096–1100
Southern FM (1975) J Mol Biol 98:503–517
St. John TP, Davis RW (1981) J Mol Biol 152:285–315
Struhl K, Stinchcomb DT, Scherer S, Davis RW (1979). Proc Natl Acad Sci USA 76:1035–1039
Szostak JW, Wu R (1980) Nature 284:426–430
Thomas PS (1980) Proc Natl Acad Sci USA 77:5201–5205
Wahl GM, Stern M, Stark GR (1979a) Proc Natl Acad Sci USA 76:3683–3687
Wahl GM, Padgett RA, Stark GR (1979b) J Biol Chem 254:8679–8689
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Fogel, S., Welch, J.W., Cathala, G. et al. Gene amplification in yeast: CUP1 copy number regulates copper resistance. Curr Genet 7, 347–355 (1983). https://doi.org/10.1007/BF00445874
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00445874