Analysis of comptothecin resistance in yeast: relevance to cancer therapy

Piero Benedetti; Youssef Benchokroun; Peter J. Houghton; Mary Ann Bjornsti

doi:10.1016/S1368-7646(98)80037-X

Analysis of comptothecin resistance in yeast: relevance to cancer therapy

Piero Benedetti, Youssef Benchokroun, Peter J. Houghton, Mary Ann Bjornsti

Research output: Contribution to journal › Review article › peer-review

7 Scopus citations

Abstract

The budding yeast Saccharomyces cerevisiae is a well defined genetic system to investigate various aspects of camptothecin (Cpt)-induced cytotoxicity. This antineoplastic agent and its derivatives specifically poison eukaryotic DNA topoisomerase I, the product of the TOP1 gene, by stabilizing a covalent enzyme-DNA intermediate. Analyses of various yeast and human top1 mutants in yeast strains deleted for TOP1 (top1Δ) have defined amino acid residues critical for enzyme function and Cpt sensitivity. Cpt cytotoxicity is also mediated by the pleiotropic drug resistance network, primarily through the action of an ABC transporter. The potential clinical relevance of these and related studies are discussed.

Original language	English (US)
Pages (from-to)	176-183
Number of pages	8
Journal	Drug Resistance Updates
Volume	1
Issue number	3
DOIs	https://doi.org/10.1016/S1368-7646(98)80037-X
State	Published - 1998
Externally published	Yes

ASJC Scopus subject areas

Infectious Diseases
Pharmacology (medical)
Oncology
Cancer Research
Pharmacology

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10.1016/S1368-7646(98)80037-X

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title = "Analysis of comptothecin resistance in yeast: relevance to cancer therapy",

abstract = "The budding yeast Saccharomyces cerevisiae is a well defined genetic system to investigate various aspects of camptothecin (Cpt)-induced cytotoxicity. This antineoplastic agent and its derivatives specifically poison eukaryotic DNA topoisomerase I, the product of the TOP1 gene, by stabilizing a covalent enzyme-DNA intermediate. Analyses of various yeast and human top1 mutants in yeast strains deleted for TOP1 (top1Δ) have defined amino acid residues critical for enzyme function and Cpt sensitivity. Cpt cytotoxicity is also mediated by the pleiotropic drug resistance network, primarily through the action of an ABC transporter. The potential clinical relevance of these and related studies are discussed.",

author = "Piero Benedetti and Youssef Benchokroun and Houghton, {Peter J.} and Bjornsti, {Mary Ann}",

year = "1998",

doi = "10.1016/S1368-7646(98)80037-X",

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AU - Benchokroun, Youssef

AU - Houghton, Peter J.

AU - Bjornsti, Mary Ann

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N2 - The budding yeast Saccharomyces cerevisiae is a well defined genetic system to investigate various aspects of camptothecin (Cpt)-induced cytotoxicity. This antineoplastic agent and its derivatives specifically poison eukaryotic DNA topoisomerase I, the product of the TOP1 gene, by stabilizing a covalent enzyme-DNA intermediate. Analyses of various yeast and human top1 mutants in yeast strains deleted for TOP1 (top1Δ) have defined amino acid residues critical for enzyme function and Cpt sensitivity. Cpt cytotoxicity is also mediated by the pleiotropic drug resistance network, primarily through the action of an ABC transporter. The potential clinical relevance of these and related studies are discussed.

AB - The budding yeast Saccharomyces cerevisiae is a well defined genetic system to investigate various aspects of camptothecin (Cpt)-induced cytotoxicity. This antineoplastic agent and its derivatives specifically poison eukaryotic DNA topoisomerase I, the product of the TOP1 gene, by stabilizing a covalent enzyme-DNA intermediate. Analyses of various yeast and human top1 mutants in yeast strains deleted for TOP1 (top1Δ) have defined amino acid residues critical for enzyme function and Cpt sensitivity. Cpt cytotoxicity is also mediated by the pleiotropic drug resistance network, primarily through the action of an ABC transporter. The potential clinical relevance of these and related studies are discussed.

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Analysis of comptothecin resistance in yeast: relevance to cancer therapy

Abstract

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