A novel strategy for identifying mutations that sensitizeDrosophilaeye development to caffeine and hydroxyurea

Abstract

This report describes a novel strategy for isolating Drosophila mutants with conditional eye phenotypes that should be generally applicable for identifying genes required for cellular responses to specific drugs. To test the strategy, we screened 3 of the 5 major chromosome arms for hydroxyurea- and (or) caffeine-sensitive (huc) mutants, and isolated mutations affecting 5 different complementation groups. Most of these were represented by single alleles; however, we also isolated multiple alleles of huc29DEgene, an essential gene that is also associated with a nonconditional pupal lethal phenotype. We also identified huc95Emutants, which are extremely sensitive to caffeine. Although huc95Eis a nonessential gene, mutant imaginal disc cells undergo caffeine-dependent apoptosis, and huc95Egene function is required for the viability of the organism when mutant larvae are exposed to levels of caffeine that controls can easily tolerate. We have mapped the cytological positions of huc29Dand huc95Eas a first step toward molecularly characterizing the relevant genes.