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Proc Natl Acad Sci U S A. Jan 1984; 81(2): 337–341.
PMCID: PMC344671

Primary structure and transcription of an amplified genetic locus: the CUP1 locus of yeast.


Copper resistance in yeast is controlled by the CUP1 locus. The level of resistance is proportional to the copy number of this locus, which can be found in up to 15 tandemly iterated copies. To elucidate the molecular mechanisms controlling the amplification and expression of the CUP1, locus, we determined its full nucleotide sequence. We have also identified and mapped two transcription units within the basic amplification unit of CUP1 in laboratory yeast strains. One of those transcription units is inducible by copper and encodes a low molecular weight copper binding protein--copper chelatin. The increased production of chelatin, due to both gene amplification and induction of transcription, leads to increased resistance of yeast cells to copper ions.

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  • BRENES-POMALES A, LINDEGREN G, LINDEGREN CC. Gene control of coppersensitivity in Saccharomyces. Nature. 1955 Oct 29;176(4487):841–842. [PubMed]
  • Hawthorne DC, Mortimer RK. Chromosome Mapping in Saccharomyces: Centromere-Linked Genes. Genetics. 1960 Aug;45(8):1085–1110. [PMC free article] [PubMed]
  • Fogel S, Welch JW. Tandem gene amplification mediates copper resistance in yeast. Proc Natl Acad Sci U S A. 1982 Sep;79(17):5342–5346. [PMC free article] [PubMed]
  • Bell GI, DeGennaro LJ, Gelfand DH, Bishop RJ, Valenzuela P, Rutter WJ. Ribosomal RNA genes of Saccharomyces cerevisiae. I. Physical map of the repeating unit and location of the regions coding for 5 S, 5.8 S, 18 S, and 25 S ribosomal RNAs. J Biol Chem. 1977 Nov 25;252(22):8118–8125. [PubMed]
  • Cramer JH, Farrelly FW, Barnitz JT, Rownd RH. Construction and restriction endonuclease mapping of hybrid plasmids containing Saccharomyces cerevisiae ribosomal DNA. Mol Gen Genet. 1977 Mar 16;151(3):229–244. [PubMed]
  • Wellauer PK, Dawid IB. The structural organization of ribosomal DNA in Drosophila melanogaster. Cell. 1977 Feb;10(2):193–212. [PubMed]
  • Glover DM, Hogness DS. A novel arrangement of the 18S and 28S sequences in a repeating unit of Drosophila melanogaster rDNA. Cell. 1977 Feb;10(2):167–176. [PubMed]
  • Wellauer PK, Dawid IB, Brown DD, Reeder RH. The molecular basis for length heterogeneity in ribosomal DNA from Xenopus laevis. J Mol Biol. 1976 Aug 25;105(4):461–486. [PubMed]
  • Carroll D, Brown DD. Adjacent repeating units of Xenopus laevis 5S DNA can be heterogeneous in length. Cell. 1976 Apr;7(4):477–486. [PubMed]
  • Manning RF, Samols DR, Gage LP. The genes for 18S, 5.8S and 28S ribosomal RNA of Bombyx mori are organized into tandem repeats of uniform length. Gene. 1978 Oct;4(2):153–166. [PubMed]
  • Schaffner W, Gross K, Telford J, Birnstiel M. Molecular analysis of the histone gene cluster of psammechinus miliaris: II. The arrangement of the five histone-coding and spacer sequences. Cell. 1976 Aug;8(4):471–478. [PubMed]
  • Cohn RH, Lowry JC, Kedes LH. Histone genes of the sea urchin (S. purpuratus) cloned in E coli: order, polarity, and strandedness of the five histone-coding and spacer regions. Cell. 1976 Sep;9(1):147–161. [PubMed]
  • Crawford RJ, Krieg P, Harvey RP, Hewish DA, Wells JR. Histone genes are clustered with a 15-kilobase repeat in the chicken genome. Nature. 1979 May 10;279(5709):132–136. [PubMed]
  • Callan HG. The organization of genetic units in chromosomes. J Cell Sci. 1967 Mar;2(1):1–7. [PubMed]
  • Buongiorno-Nardelli M, Amaldi F, Lava-Sanchez PA. Amplification as a rectification mechanism for the redundant rRNA genes. Nat New Biol. 1972 Aug 2;238(83):134–137. [PubMed]
  • Tartof KD. Unequal mitotic sister chromatid exchange and disproportionate replication as mechanisms regulating ribosomal RNA gene redundancy. Cold Spring Harb Symp Quant Biol. 1974;38:491–500. [PubMed]
  • Hinnen A, Hicks JB, Fink GR. Transformation of yeast. Proc Natl Acad Sci U S A. 1978 Apr;75(4):1929–1933. [PMC free article] [PubMed]
  • Struhl K, Stinchcomb DT, Scherer S, Davis RW. High-frequency transformation of yeast: autonomous replication of hybrid DNA molecules. Proc Natl Acad Sci U S A. 1979 Mar;76(3):1035–1039. [PMC free article] [PubMed]
  • Welch JW, Fogel S, Cathala G, Karin M. Industrial yeasts display tandem gene iteration at the CUP1 region. Mol Cell Biol. 1983 Aug;3(8):1353–1361. [PMC free article] [PubMed]
  • Premakumar R, Winge DR, Wiley RD, Rajagopalan KV. Copper-chelatin: isolation from various eucaryotic sources. Arch Biochem Biophys. 1975 Sep;170(1):278–288. [PubMed]
  • Weser U, Hartmann HJ, Fretzdorff A, Strobel GJ. Homologous copper(I)-(thiolate)2-chromophores in yeast copper thionein. Biochim Biophys Acta. 1977 Aug 23;493(2):465–477. [PubMed]
  • Prinz R, Weser U. Cuprodoxin. FEBS Lett. 1975 Jun 15;54(2):224–229. [PubMed]
  • Beach LR, Palmiter RD. Amplification of the metallothionein-I gene in cadmium-resistant mouse cells. Proc Natl Acad Sci U S A. 1981 Apr;78(4):2110–2114. [PMC free article] [PubMed]
  • Karin M, Cathala G, Nguyen-Huu MC. Expression and regulation of a human metallothionein gene carried on an autonomously replicating shuttle vector. Proc Natl Acad Sci U S A. 1983 Jul;80(13):4040–4044. [PMC free article] [PubMed]
  • Thomas PS. Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5201–5205. [PMC free article] [PubMed]
  • Weaver RF, Weissmann C. Mapping of RNA by a modification of the Berk-Sharp procedure: the 5' termini of 15 S beta-globin mRNA precursor and mature 10 s beta-globin mRNA have identical map coordinates. Nucleic Acids Res. 1979 Nov 10;7(5):1175–1193. [PMC free article] [PubMed]
  • Karin M, Richards RI. Human metallothionein genes--primary structure of the metallothionein-II gene and a related processed gene. Nature. 1982 Oct 28;299(5886):797–802. [PubMed]
  • Sanger F, Nicklen S, Coulson AR. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. [PMC free article] [PubMed]
  • Heidecker G, Messing J, Gronenborn B. A versatile primer for DNA sequencing in the M13mp2 cloning system. Gene. 1980 Jun;10(1):69–73. [PubMed]
  • Southern EM. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. [PubMed]
  • Rigby PW, Dieckmann M, Rhodes C, Berg P. Labeling deoxyribonucleic acid to high specific activity in vitro by nick translation with DNA polymerase I. J Mol Biol. 1977 Jun 15;113(1):237–251. [PubMed]
  • Corden J, Wasylyk B, Buchwalder A, Sassone-Corsi P, Kedinger C, Chambon P. Promoter sequences of eukaryotic protein-coding genes. Science. 1980 Sep 19;209(4463):1406–1414. [PubMed]
  • Zalkin H, Yanofsky C. Yeast gene TRP5: structure, function, regulation. J Biol Chem. 1982 Feb 10;257(3):1491–1500. [PubMed]
  • Zaret KS, Sherman F. DNA sequence required for efficient transcription termination in yeast. Cell. 1982 Mar;28(3):563–573. [PubMed]
  • Grunstein M, Hogness DS. Colony hybridization: a method for the isolation of cloned DNAs that contain a specific gene. Proc Natl Acad Sci U S A. 1975 Oct;72(10):3961–3965. [PMC free article] [PubMed]
  • Zamb TJ, Petes TD. Analysis of the junction between ribosomal RNA genes and single-copy chromosomal sequences in the yeast Saccharomyces cerevisiae. Cell. 1982 Feb;28(2):355–364. [PubMed]
  • Roberts JM, Buck LB, Axel R. A structure for amplified DNA. Cell. 1983 May;33(1):53–63. [PubMed]

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