When Ran binds to RCC1 (right), FRET (yellows and reds) decreases as chromatin binding increases.

When RCC1's tail gets between it and chromatin, it gets a little help from its partner, Ran, to move the tail aside, according to Hao and Macara.

RCC1 is a chromatin-binding protein essential for chromosome condensation, mitosis, and nuclear envelope assembly, and is also the only known exchange factor for the all-important Ran GTPase. RCC1 is shaped like a doughnut with a tail. Both parts of the protein have been implicated in chromatin-binding—removal of either portion weakens, but does not prevent, chromatin binding—which suggests a synergy between doughnut and tail, but the mechanistic details have been lacking.

Binding of Ran to one side of the doughnut prompts the other side to bind chromatin, but because the doughnut is a rigid structure, Ran binding cannot simply induce an allosteric change in its shape. The authors thus looked more closely at the tail's potential function. Without the tail, RCC1 lost its ability to bind to DNA, but, surprisingly, bound more strongly to histones. This suggested that the tail might, at times, obstruct the protein's histone binding site.

The authors attached FRET fluorophores to both tail and doughnut, and found that when Ran was added, FRET efficiency dropped, in keeping with a movement of the tail away from the body of the protein. The authors propose that “Ran binding swings the tail outward, exposing the belly of the doughnut where histones bind, while moving the tail closer to the DNA.” In keeping with this model, RCC1 bound to both DNA and histones more strongly in the presence of Ran. RR

Hao, Y., and I.G. Macara.
J. Cell Biol.