Analysis of comptothecin resistance in yeast: relevance to cancer therapy

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

Research output: Contribution to journalReview articlepeer-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 languageEnglish (US)
Pages (from-to)176-183
Number of pages8
JournalDrug Resistance Updates
Volume1
Issue number3
DOIs
StatePublished - Dec 1 1998
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Pharmacology
  • Cancer Research
  • Infectious Diseases
  • Pharmacology (medical)

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