Differential subcellular localization of DNA topoisomerase-1 isoforms and their roles during Caenorhabditis elegans development.

DNA topoisomerase-1 (TOP-1) resolves the topological problems associated with DNA replication, transcription and recombination by introducing temporary single-strand breaks in the DNA. Caenorhabditis elegans TOP-1 has two isoforms, TOP-1α and TOP-1β. TOP-1β is broadly localized to the nuclei of many cells at all developmental stages and concentrated in nucleoli in embryo gut and oogenic cells. However, TOP-1α is specifically localized to centrosomes, neuronal cells, excretory cells and chromosomes of germ cells in embryonic and larval stages. Reporter gene analysis also shows that top-1 transcription is highly activated in several sensory neurons, speculating the possible role of TOP-1α in neuronal development. From RNA interference (RNAi) experiments, we demonstrated that C. elegans TOP-1 is required for chromosomal segregation, germline proliferation and gonadal migration, which are all correlated with the expression and activity of TOP-1. Therefore, our findings may provide an insight into a new role of TOP-1 in development of multicellular organisms.