title: Regulation of chromatin binding by a conformational switch in the tail of the Ran exchange factor RCC1.
abstract: RCC1 is the only known exchange factor for the Ran guanosine triphosphatase and performs essential roles in nuclear transport, spindle organization, and nuclear envelope formation. RCC1 binds to chromatin through a bimodal attachment to DNA and histones, and defects in binding cause chromosome missegregation. Chromatin binding is enhanced by apo-Ran. However, the mechanism underlying this regulation has been unclear. We now demonstrate that the N-terminal tail of RCC1 is essential for association with DNA but inhibits histone binding. Apo-Ran significantly promotes RCC1 binding to both DNA and histones, and these effects are tail mediated. Using a fluorescence resonance energy transfer biosensor, we detect conformational changes in the tail of RCC1 coupled to the two binding modes and in response to interactions with Ran and importin-alpha. The biosensor also reports changes accompanying mitosis in living cells. We propose that Ran induces an allosteric conformational switch in the tail that exposes the histone-binding surface on RCC1 and facilitates association of the positively charged tail with DNA.
authors.affiliation: Department of Cell Biology, Center for Cell Signaling, University of Virginia, Charlottesville, VA 22908, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Hao
authors.forename: Ian G
authors.initials: IG
authors.lastname: Macara