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Mol Cell Biol. Dec 1995; 15(12): 6875–6883.
PMCID: PMC230942

Expression of an ATP-binding cassette transporter-encoding gene (YOR1) is required for oligomycin resistance in Saccharomyces cerevisiae.

Abstract

Semidominant mutations in the PDR1 or PDR3 gene lead to elevated resistance to cycloheximide and oligomycin. PDR1 and PDR3 have been demonstrated to encode zinc cluster transcription factors. Cycloheximide resistance mediated by PDR1 and PDR3 requires the presence of the PDR5 membrane transporter-encoding gene. However, PDR5 is not required for oligomycin resistance. Here, we isolated a gene that is necessary for PDR1- and PDR3-mediated oligomycin resistance. This locus, designated YOR1, causes a dramatic elevation in oligomycin resistance when present in multiple copies. A yor1 strain exhibits oligomycin hypersensitivity relative to an isogenic wild-type strain. In addition, loss of the YOR1 gene blocks the elevation in oligomycin resistance normally conferred by mutant forms of PDR1 or PDR3. The YOR1 gene product is predicted to be a member of the ATP-binding cassette transporter family of membrane proteins. Computer alignment indicates that Yor1p shows striking sequence similarity with multidrug resistance-associated protein, Saccharomyces cerevisiae Ycf1p, and the cystic fibrosis transmembrane conductance regulator. Use of a YOR1-lacZ fusion gene indicates that YOR1 expression is responsive to PDR1 and PDR3. While PDR5 expression is strictly dependent on the presence of PDR1 or PDR3, control of YOR1 expression has a significant PDR1/PDR3-independent component. Taken together, these data indicate that YOR1 provides the link between transcriptional regulation by PDR1 and PDR3 and oligomycin resistance of yeast cells.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Alani E, Cao L, Kleckner N. A method for gene disruption that allows repeated use of URA3 selection in the construction of multiply disrupted yeast strains. Genetics. 1987 Aug;116(4):541–545. [PMC free article] [PubMed]
  • Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ. Basic local alignment search tool. J Mol Biol. 1990 Oct 5;215(3):403–410. [PubMed]
  • Balzi E, Chen W, Ulaszewski S, Capieaux E, Goffeau A. The multidrug resistance gene PDR1 from Saccharomyces cerevisiae. J Biol Chem. 1987 Dec 15;262(35):16871–16879. [PubMed]
  • Balzi E, Goffeau A. Multiple or pleiotropic drug resistance in yeast. Biochim Biophys Acta. 1991 Mar 4;1073(2):241–252. [PubMed]
  • Balzi E, Goffeau A. Yeast multidrug resistance: the PDR network. J Bioenerg Biomembr. 1995 Feb;27(1):71–76. [PubMed]
  • Balzi E, Wang M, Leterme S, Van Dyck L, Goffeau A. PDR5, a novel yeast multidrug resistance conferring transporter controlled by the transcription regulator PDR1. J Biol Chem. 1994 Jan 21;269(3):2206–2214. [PubMed]
  • Bissinger PH, Kuchler K. Molecular cloning and expression of the Saccharomyces cerevisiae STS1 gene product. A yeast ABC transporter conferring mycotoxin resistance. J Biol Chem. 1994 Feb 11;269(6):4180–4186. [PubMed]
  • Boeke JD, LaCroute F, Fink GR. A positive selection for mutants lacking orotidine-5'-phosphate decarboxylase activity in yeast: 5-fluoro-orotic acid resistance. Mol Gen Genet. 1984;197(2):345–346. [PubMed]
  • Cheng SH, Gregory RJ, Marshall J, Paul S, Souza DW, White GA, O'Riordan CR, Smith AE. Defective intracellular transport and processing of CFTR is the molecular basis of most cystic fibrosis. Cell. 1990 Nov 16;63(4):827–834. [PubMed]
  • Cole SP, Bhardwaj G, Gerlach JH, Mackie JE, Grant CE, Almquist KC, Stewart AJ, Kurz EU, Duncan AM, Deeley RG. Overexpression of a transporter gene in a multidrug-resistant human lung cancer cell line. Science. 1992 Dec 4;258(5088):1650–1654. [PubMed]
  • Decottignies A, Lambert L, Catty P, Degand H, Epping EA, Moye-Rowley WS, Balzi E, Goffeau A. Identification and characterization of SNQ2, a new multidrug ATP binding cassette transporter of the yeast plasma membrane. J Biol Chem. 1995 Jul 28;270(30):18150–18157. [PubMed]
  • Delahodde A, Delaveau T, Jacq C. Positive autoregulation of the yeast transcription factor Pdr3p, which is involved in control of drug resistance. Mol Cell Biol. 1995 Aug;15(8):4043–4051. [PMC free article] [PubMed]
  • Delaveau T, Delahodde A, Carvajal E, Subik J, Jacq C. PDR3, a new yeast regulatory gene, is homologous to PDR1 and controls the multidrug resistance phenomenon. Mol Gen Genet. 1994 Sep 1;244(5):501–511. [PubMed]
  • Devereux J, Haeberli P, Smithies O. A comprehensive set of sequence analysis programs for the VAX. Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387–395. [PMC free article] [PubMed]
  • Dexter D, Moye-Rowley WS, Wu AL, Golin J. Mutations in the yeast PDR3, PDR4, PDR7 and PDR9 pleiotropic (multiple) drug resistance loci affect the transcript level of an ATP binding cassette transporter encoding gene, PDR5. Genetics. 1994 Feb;136(2):505–515. [PMC free article] [PubMed]
  • Doige CA, Ames GF. ATP-dependent transport systems in bacteria and humans: relevance to cystic fibrosis and multidrug resistance. Annu Rev Microbiol. 1993;47:291–319. [PubMed]
  • Endicott JA, Ling V. The biochemistry of P-glycoprotein-mediated multidrug resistance. Annu Rev Biochem. 1989;58:137–171. [PubMed]
  • Gietz D, St Jean A, Woods RA, Schiestl RH. Improved method for high efficiency transformation of intact yeast cells. Nucleic Acids Res. 1992 Mar 25;20(6):1425–1425. [PMC free article] [PubMed]
  • Gros P, Croop J, Housman D. Mammalian multidrug resistance gene: complete cDNA sequence indicates strong homology to bacterial transport proteins. Cell. 1986 Nov 7;47(3):371–380. [PubMed]
  • Guan KL, Dixon JE. Eukaryotic proteins expressed in Escherichia coli: an improved thrombin cleavage and purification procedure of fusion proteins with glutathione S-transferase. Anal Biochem. 1991 Feb 1;192(2):262–267. [PubMed]
  • Higgins CF. ABC transporters: from microorganisms to man. Annu Rev Cell Biol. 1992;8:67–113. [PubMed]
  • Hirata D, Yano K, Miyahara K, Miyakawa T. Saccharomyces cerevisiae YDR1, which encodes a member of the ATP-binding cassette (ABC) superfamily, is required for multidrug resistance. Curr Genet. 1994 Oct;26(4):285–294. [PubMed]
  • Hoffman CS, Winston F. A ten-minute DNA preparation from yeast efficiently releases autonomous plasmids for transformation of Escherichia coli. Gene. 1987;57(2-3):267–272. [PubMed]
  • Hyde SC, Emsley P, Hartshorn MJ, Mimmack MM, Gileadi U, Pearce SR, Gallagher MP, Gill DR, Hubbard RE, Higgins CF. Structural model of ATP-binding proteins associated with cystic fibrosis, multidrug resistance and bacterial transport. Nature. 1990 Jul 26;346(6282):362–365. [PubMed]
  • Ito H, Fukuda Y, Murata K, Kimura A. Transformation of intact yeast cells treated with alkali cations. J Bacteriol. 1983 Jan;153(1):163–168. [PMC free article] [PubMed]
  • Katzmann DJ, Burnett PE, Golin J, Mahé Y, Moye-Rowley WS. Transcriptional control of the yeast PDR5 gene by the PDR3 gene product. Mol Cell Biol. 1994 Jul;14(7):4653–4661. [PMC free article] [PubMed]
  • Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. [PubMed]
  • Leier I, Jedlitschky G, Buchholz U, Cole SP, Deeley RG, Keppler D. The MRP gene encodes an ATP-dependent export pump for leukotriene C4 and structurally related conjugates. J Biol Chem. 1994 Nov 11;269(45):27807–27810. [PubMed]
  • Leonard PJ, Rathod PK, Golin J. Loss of function mutation in the yeast multiple drug resistance gene PDR5 causes a reduction in chloramphenicol efflux. Antimicrob Agents Chemother. 1994 Oct;38(10):2492–2494. [PMC free article] [PubMed]
  • Leppert G, McDevitt R, Falco SC, Van Dyk TK, Ficke MB, Golin J. Cloning by gene amplification of two loci conferring multiple drug resistance in Saccharomyces. Genetics. 1990 May;125(1):13–20. [PMC free article] [PubMed]
  • LOWRY OH, ROSEBROUGH NJ, FARR AL, RANDALL RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed]
  • Mann C, Buhler JM, Treich I, Sentenac A. RPC40, a unique gene for a subunit shared between yeast RNA polymerases A and C. Cell. 1987 Feb 27;48(4):627–637. [PubMed]
  • Meyers S, Schauer W, Balzi E, Wagner M, Goffeau A, Golin J. Interaction of the yeast pleiotropic drug resistance genes PDR1 and PDR5. Curr Genet. 1992 May;21(6):431–436. [PubMed]
  • Ooi BG, Novitski CE, Nagley P. DNA sequence analysis of the oli1 gene reveals amino acid changes in mitochondrial ATPase subunit 9 from oligomycin-resistant mutants of Saccharomyces cerevisiae. Eur J Biochem. 1985 Nov 4;152(3):709–714. [PubMed]
  • Ortiz DF, Ruscitti T, McCue KF, Ow DW. Transport of metal-binding peptides by HMT1, a fission yeast ABC-type vacuolar membrane protein. J Biol Chem. 1995 Mar 3;270(9):4721–4728. [PubMed]
  • Riles L, Dutchik JE, Baktha A, McCauley BK, Thayer EC, Leckie MP, Braden VV, Depke JE, Olson MV. Physical maps of the six smallest chromosomes of Saccharomyces cerevisiae at a resolution of 2.6 kilobase pairs. Genetics. 1993 May;134(1):81–150. [PMC free article] [PubMed]
  • Riordan JR, Rommens JM, Kerem B, Alon N, Rozmahel R, Grzelczak Z, Zielenski J, Lok S, Plavsic N, Chou JL, et al. Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA. Science. 1989 Sep 8;245(4922):1066–1073. [PubMed]
  • Riordan JR, Deuchars K, Kartner N, Alon N, Trent J, Ling V. Amplification of P-glycoprotein genes in multidrug-resistant mammalian cell lines. Nature. 316(6031):817–819. [PubMed]
  • Roninson IB, Chin JE, Choi KG, Gros P, Housman DE, Fojo A, Shen DW, Gottesman MM, Pastan I. Isolation of human mdr DNA sequences amplified in multidrug-resistant KB carcinoma cells. Proc Natl Acad Sci U S A. 1986 Jun;83(12):4538–4542. [PMC free article] [PubMed]
  • Schmitt ME, Brown TA, Trumpower BL. A rapid and simple method for preparation of RNA from Saccharomyces cerevisiae. Nucleic Acids Res. 1990 May 25;18(10):3091–3092. [PMC free article] [PubMed]
  • Subik J, Ulaszewski S, Goffeau A. Genetic mapping of nuclear mucidin resistance mutations in Saccharomyces cerevisiae. A new pdr locus on chromosome II. Curr Genet. 1986;10(9):665–670. [PubMed]
  • Szczypka MS, Wemmie JA, Moye-Rowley WS, Thiele DJ. A yeast metal resistance protein similar to human cystic fibrosis transmembrane conductance regulator (CFTR) and multidrug resistance-associated protein. J Biol Chem. 1994 Sep 9;269(36):22853–22857. [PubMed]
  • Towbin H, Staehelin T, Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350–4354. [PMC free article] [PubMed]
  • Tsui LC. The spectrum of cystic fibrosis mutations. Trends Genet. 1992 Nov;8(11):392–398. [PubMed]
  • Walker JE, Saraste M, Runswick MJ, Gay NJ. Distantly related sequences in the alpha- and beta-subunits of ATP synthase, myosin, kinases and other ATP-requiring enzymes and a common nucleotide binding fold. EMBO J. 1982;1(8):945–951. [PMC free article] [PubMed]
  • Welsh MJ, Smith AE. Molecular mechanisms of CFTR chloride channel dysfunction in cystic fibrosis. Cell. 1993 Jul 2;73(7):1251–1254. [PubMed]
  • Wu A, Wemmie JA, Edgington NP, Goebl M, Guevara JL, Moye-Rowley WS. Yeast bZip proteins mediate pleiotropic drug and metal resistance. J Biol Chem. 1993 Sep 5;268(25):18850–18858. [PubMed]

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