Analysis of second-site mutations that suppress the multiple drug resistance phenotype of the yeast PDR1-7 allele

Thomas M. McGuire; Elvira Carvajal; David Katzmann; Marisa Wagner; W. Scott Moye-Rowley; André Goffeau; John Golin

doi:10.1016/0378-1119(95)00663-X

Analysis of second-site mutations that suppress the multiple drug resistance phenotype of the yeast PDR1-7 allele

Thomas M. McGuire, Elvira Carvajal, David Katzmann, Marisa Wagner, W. Scott Moye-Rowley, André Goffeau, John Golin

Biochemistry and Molecular Biology

Research output: Contribution to journal › Article › peer-review

7 Scopus citations

Abstract

The yeast PDR1 locus encodes a member of the C6 zinc cluster family of transcriptional regulatory proteins. Among the targets of PDR1 is the yeast PDR5 locus. The product of this gene is a member of the ATP-binding cassette (ABC) transmembrane protein family and plays a major role in inhibitor efflux. Mutations in PDR1 affect the relative level of PDR5 transcript and can therefore result in increased or decreased drug resistance. We isolated three second-site suppressors of PDR1-7 semidominant hyper-resistant mutation. These mutants were drug hypersensitive, as compared with isogenic controls. Two of the three mutations contained alterations in a putative DNA-binding domain. Significantly, the mutant proteins exhibited reduced DNA-binding capacity.

Original language	English (US)
Pages (from-to)	151-155
Number of pages	5
Journal	Gene
Volume	167
Issue number	1-2
DOIs	https://doi.org/10.1016/0378-1119(95)00663-X
State	Published - Dec 29 1995

Keywords

ABC
ATP-binding cassette
PDR genes
Saccharomyces cerevisiae
transcription factor
transmembrane

ASJC Scopus subject areas

Genetics

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10.1016/0378-1119(95)00663-X

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title = "Analysis of second-site mutations that suppress the multiple drug resistance phenotype of the yeast PDR1-7 allele",

abstract = "The yeast PDR1 locus encodes a member of the C6 zinc cluster family of transcriptional regulatory proteins. Among the targets of PDR1 is the yeast PDR5 locus. The product of this gene is a member of the ATP-binding cassette (ABC) transmembrane protein family and plays a major role in inhibitor efflux. Mutations in PDR1 affect the relative level of PDR5 transcript and can therefore result in increased or decreased drug resistance. We isolated three second-site suppressors of PDR1-7 semidominant hyper-resistant mutation. These mutants were drug hypersensitive, as compared with isogenic controls. Two of the three mutations contained alterations in a putative DNA-binding domain. Significantly, the mutant proteins exhibited reduced DNA-binding capacity.",

keywords = "ABC, ATP-binding cassette, PDR genes, Saccharomyces cerevisiae, transcription factor, transmembrane",

author = "McGuire, {Thomas M.} and Elvira Carvajal and David Katzmann and Marisa Wagner and Moye-Rowley, {W. Scott} and Andr{\'e} Goffeau and John Golin",

note = "Funding Information: This work was supported by NIH grants GM49825 (W.S.M.-R.) and GM41875 (J.G.), NSF grant MCB-9307962 (J.G.) and CNPqRHAE (E.C.).{"}",

year = "1995",

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doi = "10.1016/0378-1119(95)00663-X",

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T1 - Analysis of second-site mutations that suppress the multiple drug resistance phenotype of the yeast PDR1-7 allele

AU - McGuire, Thomas M.

AU - Carvajal, Elvira

AU - Katzmann, David

AU - Wagner, Marisa

AU - Moye-Rowley, W. Scott

AU - Goffeau, André

AU - Golin, John

N1 - Funding Information: This work was supported by NIH grants GM49825 (W.S.M.-R.) and GM41875 (J.G.), NSF grant MCB-9307962 (J.G.) and CNPqRHAE (E.C.)."

PY - 1995/12/29

Y1 - 1995/12/29

N2 - The yeast PDR1 locus encodes a member of the C6 zinc cluster family of transcriptional regulatory proteins. Among the targets of PDR1 is the yeast PDR5 locus. The product of this gene is a member of the ATP-binding cassette (ABC) transmembrane protein family and plays a major role in inhibitor efflux. Mutations in PDR1 affect the relative level of PDR5 transcript and can therefore result in increased or decreased drug resistance. We isolated three second-site suppressors of PDR1-7 semidominant hyper-resistant mutation. These mutants were drug hypersensitive, as compared with isogenic controls. Two of the three mutations contained alterations in a putative DNA-binding domain. Significantly, the mutant proteins exhibited reduced DNA-binding capacity.

AB - The yeast PDR1 locus encodes a member of the C6 zinc cluster family of transcriptional regulatory proteins. Among the targets of PDR1 is the yeast PDR5 locus. The product of this gene is a member of the ATP-binding cassette (ABC) transmembrane protein family and plays a major role in inhibitor efflux. Mutations in PDR1 affect the relative level of PDR5 transcript and can therefore result in increased or decreased drug resistance. We isolated three second-site suppressors of PDR1-7 semidominant hyper-resistant mutation. These mutants were drug hypersensitive, as compared with isogenic controls. Two of the three mutations contained alterations in a putative DNA-binding domain. Significantly, the mutant proteins exhibited reduced DNA-binding capacity.

KW - ABC

KW - ATP-binding cassette

KW - PDR genes

KW - Saccharomyces cerevisiae

KW - transcription factor

KW - transmembrane

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AN - SCOPUS:0029618391

SN - 0378-1119

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JO - Gene

JF - Gene

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ER -

Analysis of second-site mutations that suppress the multiple drug resistance phenotype of the yeast PDR1-7 allele

Abstract

Keywords

ASJC Scopus subject areas

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