The antitumor activity of bleomycin is associated with its ability to produce DNA lesions. The cellular process that repairs bleomycin-induced DNA lesions is not entirely clear. To understand how these DNA lesions are repaired in eukaryotic cells, we used mini Tn3 : : LEU2 :: LacZ transposon mutagenesis to isolate yeast mutants that were hypersensitive to bleomycin. One of the mutants, HCY69, was characterized further and found to be 4- and 3-fold more sensitive, respectively, to bleomycin and hydrogen peroxide, as compared to the parent. The mutant displayed parental resistance to a variety of other DNA-damaging agents. Plasmid rescue and DNA sequence analysis revealed that the transposon interrupted the OXA1 gene, which encodes a protein required to process one of the subunits, cox II, of the cytochrome oxidase complex in mitochondria. A plasmid carrying the native OXA1 gene fully restored drug resistance to strain HCY69. Our data strongly suggest that functional mitochondria are required for cellular protection against the toxic effects of bleomycin.
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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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