We previously established a genotoxicity detection system based on the transcriptional response of the yeast RNR3 gene to DNA damage. In order to further improve its sensitivity to genotoxicants, we have attempted to increase cell permeability by removing cell wall mannoproteins (CWPs). Here, we report that selected deletion of pleiotropic drug resistance (PDR) genes encoding membrane efflux transporters also enhanced cellular sensitivity to treatment by various genotoxic agents. Furthermore, we have validated our hypothesis that PDR and CWP protect cells through different mechanisms by demonstrating that simultaneous inactivation of the above two pathways resulted in a synergistic enhancement of assay sensitivity as measured by RNR3-lacZ expression and that this effect is at the cell permeability level. The quadruple mutation results in RNR3-lacZ assay sensitivity to tested chemicals that apparently surpasses the industry standard Ames test. We argue that this hyperpermeable yeast mutant strain would be suitable for other chemical-based genotoxic assays.
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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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