Several 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.
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Evidence ID | Analyze ID | Gene/Complex | Systematic Name/Complex Accession | Qualifier | Gene Ontology Term ID | Gene Ontology Term | Aspect | Annotation Extension | Evidence | Method | Source | Assigned On | Reference |
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Evidence ID | Analyze ID | Gene | Gene Systematic Name | Phenotype | Experiment Type | Experiment Type Category | Mutant Information | Strain Background | Chemical | Details | Reference |
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Evidence ID | Analyze ID | Gene | Gene Systematic Name | Disease Ontology Term | Disease Ontology Term ID | Qualifier | Evidence | Method | Source | Assigned On | Reference |
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Evidence ID | Analyze ID | Regulator | Regulator Systematic Name | Target | Target Systematic Name | Direction | Regulation of | Happens During | Regulator Type | Direction | Regulation Of | Happens During | Method | Evidence | Strain Background | Reference |
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Site | Modification | Modifier | Source | Reference |
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Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Allele | Assay | Annotation | Action | Phenotype | SGA score | P-value | Source | Reference | Note |
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Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Assay | Annotation | Action | Modification | Source | Reference | Note |
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Complement ID | Locus ID | Gene | Species | Gene ID | Strain background | Direction | Details | Source | Reference |
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Evidence ID | Analyze ID | Dataset | Description | Keywords | Number of Conditions | Reference |
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