Drug-induced haploinsufficiency of fission yeast provides a powerful tool for identification of drug targets

Abstract

Genome-wide systematic deletion mutants were generated using a PCR-based targeted mutagenesis of Schizosaccharomyces pombe. In a drug-sensitivity assay using thiabendazole (TBZ), an inhibitor of microtubule assembly, a heterozygous nda2 mutant (nda2+/nda2-), deleting one copy of nda2 encoding the microtubule subunit alpha 1 demonstrated a distinct sensitivity to TBZ, indicating TBZ-induced haploinsufficiency. This result suggests that profiling drug-induced haploinsufficiency can be exploited to identify target genes for drugs and discover new drugs.