To identify novel genes that mediate cellular resistance to cisplatin, we have screened the collection of Saccharomyces cerevisiae deletion strains. We have found reproducibly 22 genes/open reading frames (ORF), which when deleted, confer resistance to cisplatin at a concentration that is lethal to wild-type cells. Complementation of individual deletion strains with the corresponding wild-type gene abolished cisplatin resistance, confirming that specific gene deletions caused the resistance. Twenty of the genes/ORFs identified have not been previously linked to cisplatin resistance and belong to several distinct functional groups. Major functional groups encode proteins involved in nucleotide metabolism, mRNA catabolism, RNA-polymerase-II-dependent gene regulation and vacuolar transport systems. In addition, proteins that function in ubiquitination, sphingolipid biogenesis, cyclic AMP-dependent signaling, DNA repair, and genome stability are also associated with cisplatin resistance. More than half of the identified genes are known to have sequences or functional homology to mammalian counterparts. Some deletion strains are cross-resistant to selected cytotoxic agents whereas hypersensitive to others. The sensitivity of certain resistant strains to other cytotoxic agents suggests that our findings may point to particular drug combinations that can overcome resistance caused by inactivation of specific genes.
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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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