The natural product neocarzinostatin (NCS), a protein-small molecule complex, exhibits potent antiproliferative activity in mammalian cells but has little apparent effect on the growth of the unicellular eukaryotic organism, Saccharomyces cerevisiae. Here, we show by whole-genome transcription profiling experiments that incubation of S. cerevisiae with NCS leads to dramatic and wide-ranging modifications in the expression profile of yeast genes. Approximately 18% of yeast transcripts are altered by 2-fold or more within 4 h of treatment with NCS. Analysis of the observed transcription profile provides evidence that yeast rapidly and continuously overexpress multiple DNA-damage repair genes during NCS exposure. Perhaps to meet the energetic requirements of continuous DNA-damage repair, yeast cells enter respiration upon prolonged exposure to NCS, although grown in nutrient-rich medium. The NCS protein component is readily transported into S. cerevisiae, as demonstrated by fluorescence microscopy of yeast treated with fluorescently labeled NCS. Transcription profiling experiments with neocarzinostatin protein alone implicate a specific resistance mechanism in yeast that targets the NCS protein component, one involving the nonclassical export pathway. These experiments provide a detailed picture of the effects of exposure to NCS upon yeast and the mechanisms they engage as a response to this protein-small molecule DNA-damaging agent.
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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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Evidence ID | Analyze ID | File | Description |
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