title: Microarray-based target identification using drug hypersensitive fission yeast expressing ORFeome.
abstract: Identification of the cellular target of small molecules is a major challenge to developing biological tools and drug leads. Here we report a novel microarray-based system for identification of the target or the target pathway of small molecules using a set of drug-hypersensitive fission yeast strains that collectively overexpress each gene in the open reading frame-ome. The major advantage of this method is that it provides genome-wide interrogation but requires a relatively small amount of the test compound. Using this system, we identified 28 genes linked to etoposide sensitivity, which included genes for the drug target topoisomerase II and other plausible factors that regulate etoposide tolerance. Thus, our approach can accelerate the process of target identification of small molecules, which has the potential to reveal highly conserved genes of clinical relevance.
authors.affiliation: Chemical Genetics Laboratory, RIKEN Advanced Science Institute, Wako, Saitama 351-0198, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Arita
authors.forename: Shinichi
authors.initials: S
authors.lastname: Nishimura
authors.forename: Akihisa
authors.initials: A
authors.lastname: Matsuyama
authors.forename: Yoko
authors.initials: Y
authors.lastname: Yashiroda
authors.forename: Takeo
authors.initials: T
authors.lastname: Usui
authors.forename: Charles
authors.initials: C
authors.lastname: Boone
authors.forename: Minoru
authors.initials: M
authors.lastname: Yoshida
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D020126:Brefeldin A / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D025141:Drug Resistance, Fungal / Q000235:genetics; D005047:Etoposide / Q000494:pharmacology; D015725:Fluconazole / Q000494:pharmacology; D005656:Fungal Proteins / Q000235:genetics; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects; D016681:Genome, Fungal / Q000235:genetics; D008825:Miconazole / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D016366:Open Reading Frames / Q000235:genetics*; D012568:Schizosaccharomyces / Q000187:drug effects* / Q000235:genetics* / Q000254:growth & development; D015262:Xenobiotics / Q000494:pharmacology*
chemical_list: D000935:Antifungal Agents; D000972:Antineoplastic Agents, Phytogenic; D005656:Fungal Proteins; D015262:Xenobiotics; D020126:Brefeldin A; D005047:Etoposide; D008825:Miconazole; D015725:Fluconazole