Ran sticks a GEF to chromatin

Gradients of the small GTPase Ran are important throughout the cell cycle. High nuclear RanGTP concentrations in interphase cells regulate nuclear transport. During mitosis, chromosome-localized RanGTP releases spindle assembly factors from sequestration by importins. On page 635, Li et al. demonstrate that RanGTP accumulates at chromosomes because the complex of Ran and its guanine nucleotide exchange factor (GEF) binds strongly to chromatin.

GTP-bound Ran is produced by the GEF RCC1, which binds only weakly to histones. Using a GFP-tagged version, the authors show that RCC1 is highly mobile and exchanges rapidly between free and chromatin-bound states. As RCC1 has strong GEF activity in the presence or absence of chromatin, the authors were interested in determining how RanGTP production is limited to chromosomes. They found that Ran-bound RCC1...