mus304 encodes a novel DMA damage checkpoint protein required during Drosophila development

Checkpoints block cell cycle progression in eukaryotic cells exposed to DNA damaging agents. We show that several Drosophila homologs of checkpoint ge nes, mei-41, grapes, and 14-3-3 epsilon, regulate a DNA damage checkpoint i n the developing eye. We have used this assay to show that the mutagen-sens itive gene mus304 is also required for this checkpoint. mus304 encodes a no vel coiled-coil domain protein, which is targeted to the cytoplasm. Similar to mei-41, mus304 is required for chromosome break repair and for genomic stability. mus304 animals also exhibit three developmental defects, abnorma l bristle morphology, decreased meiotic recombination, and arrested embryon ic development. We suggest that these phenotypes reflect distinct developme ntal consequences of a single underlying checkpoint defect. Similar mechani sms may account for the puzzling array of symptoms observed in humans with mutations in the ATM tumor suppressor gene.