In this proposal, the overall aim is to determine the role of small GTP-binding proteins in the regulation of mitosis. A small regulator for GTP-binding proteins, called a GDP Dissociation Inhibitor (GDI), has been identified from Drosophila melanogaster, through the developmental mutant known as quartet. In quartet, GDI fails to undergo a post-translational modification, and processes regulated by GTP-binding proteins are altered. Prominent among the anomalies in quartet are changes in mitotic behavior; mitotic chromosomal separation is blocked. Thus, chromosomal separation in mitosis may involve small GTP-binding proteins. %%% Mitosis is the process by which already-replicated chromosomes align, split apart, and then separate into two groups in an orderly fashion. Mitosis is similar in widely divergent cells throughout the eukaryotic realm, but our understanding of this process is not well-developed. The increased availablity of conditional mutants that exhibit anomalous entry into or progression through mitosis have proven to be powerful tools with which to dissect the mechanisms by which chromosomes move. In this project, a mutant of Drosophila exhibits anomalous progression through mitosis. The underlying mechanism for this block to chromosomal separation appears to be linked to a family of regulatory proteins that have heretofore not been linked to the process. This work has the potential to provide important clues about the regulatory components that control chromosomal separation in all higher organisms.
