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Title

Promoter-specific inhibition of transcription by daunorubicin in Saccharomyces cerevisiae

AuthorsMarín, Silvia; Mansilla, Sylvia CSIC ORCID; García-Reyero, Natàlia; Rojas, Marta; Portugal, José CSIC ORCID ; Piña, Benjamín CSIC ORCID
KeywordsAnthracyclines
Anti-cancer treatment
DNA-intercalating drug
ERG6
Semi-quantitative reverse transcriptase (RT) PCR
Issue Date15-Nov-2002
PublisherPortland Press
CitationBiochemical Journal 368(1):131-136 (2002)
AbstractSeveral anti-tumour drugs exert some of their cytotoxic effects by direct binding to DNA, thus inhibiting the transcription of certain genes. We analysed the influence of the anti-tumour antibiotic daunorubicin on the transcription of different genes in vivo using the budding yeast Saccharomyces cerevisiae. Daunorubicin only affected wild-type yeast strains at very high concentrations; however, erg6 mutant strains (but not pdr1, pdr3 or pdr5 strains) were sensitive to daunorubicin at low micromolar concentrations. In Delta erg6 strains, daunorubicin inhibited the galactose-induced transcription by Gal4p in a specific manner, since the transcription of identical reporters driven by other activators (either constitutive or inducible) was not inhibited. The drug concentrations at which Gal4p function was inhibited did not affect cell growth or viability. Furthermore, daunorubicin inhibited the growth in galactose and the transcriptional induction of resident Gal4p-driven genes upon galactose addition, two processes absolutely dependent on Gal4p function. We propose that daunorubicin and some transcription factors compete for DNA sequences encompassing CpG steps, and that this is the main determinant of the effects of the drug on transcription in vivo. Our approach may foster the development of anti-tumour drugs with more specific mechanisms of action.
Description6 pages, 3 figures, 2 tables.-- PMID: 12164785 [PubMed].-- PMCID: PMC1222970.-- Available online Aug 7, 2002.
Publisher version (URL)http://dx.doi.org/10.1042/BJ20020724
URIhttp://hdl.handle.net/10261/27426
DOI10.1042/BJ20020724
ISSN0264-6021
E-ISSN1470-8728
Appears in Collections:(IDAEA) Artículos

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