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PMID: 2160400 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Cloning by gene amplification of two loci conferring multiple drug resistance in Saccharomyces.

Genetics ·Vol. 125 ·No. 1 ·1990-05-00 ·Pages 13-20

Leppert G, McDevitt R, Falco SC, Van Dyk TK, Ficke MB, Golin J

Abstract

Yeast DNA fragments that confer multiple drug resistance when amplified were isolated. Cells containing a yeast genomic library cloned in the high copy autonomously replicating vector, YEp24, were plated on medium containing cycloheximide. Five out of 100 cycloheximide-resistant colonies were cross-resistant to the unrelated inhibitor, sulfometuron methyl, due to a plasmid-borne resistance determinant. The plasmids isolated from these resistant clones contained two nonoverlapping regions in the yeast genome now designated PDR4 and PDR5 (for pleiotropic drug resistant). PDR4 was mapped to chromosome XIII, 31.5 cM from LYS7 and 9 cM from the centromere. PDR4 was mapped to chromosome XV between ADE2 and H1S3. Genetic analysis demonstrated that at least three tightly linked genes (PDR5, PDR2 and SMR3) that mediate resistance to inhibitors are located in this region. Insertion mutations in the either PDR4 or PDR5 genes are not lethal, but the insertion in PDR5 results in a drug-hypersensitive phenotype.

MeSH Terms
Acetolactate Synthase/antagonists & inhibitors Chromosome Mapping Cloning, Molecular Cycloheximide/pharmacology DNA Transposable Elements Drug Resistance, Microbial/genetics Gene Amplification Genes, Fungal Genetic Linkage Phenotype Plasmids Restriction Mapping Saccharomyces cerevisiae/drug effects,genetics Sulfonylurea Compounds/pharmacology Transformation, Genetic
Chemicals
DNA Transposable Elements Sulfonylurea Compounds Cycloheximide Acetolactate Synthase sulfometuron methyl
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Leppert G
Department of Biology, Catholic University of America, Washington, D.C. 20064.
McDevitt R
Falco S C
Van Dyk T K
Ficke M B
Golin J
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Article Info
Journal
Genetics
Abbr.
Genetics
ISSN
0016-6731
DOI
10.1093/genetics/125.1.13
Published
1990-05-00
Pages
13-20
Language
English
Region
United States
NLM ID
0374636
PMCID
PMC1203995
Subset
IM
Grants
NIGMS NIH HHS · GM41875 · United States
External Links
PubMed source DOI: 10.1093/genetics/125.1.13 PMC Full Text View journal details
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