96-30675 D'Eustachio Progression of eukaryotic cells through the cell cycle, except at the onset of embryonic development, is regulated by checkpoints: at initiation of DNA replication, and entry into and exit from mitosis. Ran, a small GTP-binding and -hydrolyzing protein, modulates several aspects of the cell cycle progression, presumably by linking them through the intracellular trafficking of macromolecules. Ran BP1 and Ran GAP/Rna1 attenuate the Ran GTPase switch. The genes that encode these proteins have been cloned and sequenced and functional defects of these proteins have been identified in vivo. The Ran GTPase has been linked to the regulation of mRNA export from the nucleus. This activity of Ran GTPase is regulated by RanBP1. The goals of this project are: to characterize the interactions of RanBP1 with Ran and with RanGAP/Rna1 in vitro, using wild-type and mutated RanBP1; to identify additional proteins that interact with the switch through RanBP1 and RanGAP/Rna1, using the yeast interaction trap system; and to define functions of RanBP1 domains in vivo by characterizing the phenotypes of fission yeast strains whose wild-type RanBP1 genes have been replaced by mutant constructs. %%% Progression of eukaryotic cells through the cell cycle, except at the onset of embryonic development, is regulated by checkpoints: at initiation of DNA replication, and entry into and exit from mitosis. Ran, a small GTP-binding and -hydrolyzing protein, modulates several aspects of the cell cycle progression, presumably by linking them through the intracellular trafficking of macromolecules. Little is known about the molecular mechanism of how Ran controls the progression of the cell cycle. ***
