Essential functions of DNA topoisomerase I in Drosophila melanogaster

AbstractDNA topoisomerase I (topo I) is an essential enzyme involved in replication, transcription, and recombination. To probe the functions of topo I during Drosophila development, we used topl-deficient flies with heat-shock-inducible topl transgenes and were able to observe both zygotic and maternal functions of topl. A critical period for the zygotic function is in the late larval and early pupal stages. Topo I is required for larval growth and cell proliferation in imaginal disc tissues. The maternal functions consist of two aspects: oogenesis and early embryogenesis. During oogenesis, topo I is detected in the nuclei of early germ-line cells and follicle cells. The mutant ovary exhibits abnormal proliferation and defective nuclear morphology in these cells. There are extranumeral germ-line cells in individual egg chambers, while the follicle cells are underreplicated. Topo I is also stored maternally in early embryos. It localizes to the nuclei during interphase and prophase, but disperses into the cytoplasm at metaphase. Embryos from the mutant mother frequently show disrupted nuclear divisions with defects in chromosome condensation and segregation. The cytological and genetic analysis of the topl mutant demonstrates that in Drosophila, topo I plays critical roles in many developmental stages active in cell proliferation