KIF4 helps mitotic chromosomes get in shape

KIF4 helps mitotic chromosomes get in shape T hough chromosomes spend most of their time occupying amorphous territories in interphase nu-clei, we typically picture them as the compact X-shaped structures that form during mitosis. Chromosomes adopt this conformation to avoid becoming entangled as they segregate into daughter cells, but how mitotic chromatin condenses into the correct shape is unclear. Samejima et al. identify an important role for the kine-sin motor KIF4 in this process (1). Condensin complexes and the DNA-remodeling enzyme topoisomerase II␣ (topo II␣) help organize mitotic chromatin, but cells lacking these proteins still form recognizable mitotic chromosomes (2, 3). This suggests that an additional factor— what Bill Earnshaw from the University of Edinburgh calls a regulator of chromosome architecture (RCA)—is critical for chromosome condensation (4). A candidate for the RCA role is the DNA-binding kinesin motor KIF4, which interacts with condensin and localizes to the arms of mitotic chromosomes. Earnshaw and colleagues , led by postdoc Kumiko Samejima, therefore decided to investigate KIF4's function in chromatin organization (1). Samejima et al. found that KIF4 and the core con-densin subunit SMC2 rely on each other for their lo-calization on chromosome arms. At fi rst glance, mitotic chromosomes appeared normal in KIF4-defi cient cells, but treatment with a mildly hypotonic solution to resolve individual chromosomes revealed that they were fatter and shorter, and sister kinetochores were spaced farther apart than normal. Furthermore, when mitotic chromosomes were repeatedly unrav-eled and refolded, wild-type chromosomes " remembered " their shape and re-condensed efficiently, but chromosomes lacking KIF4 became disorganized , indicating that they had lost their structural integrity. The mitotic chromosomes of condensin-defi cient cells are also short and fat, and their structural integrity is even more compromised. " So KIF4 and condensin somehow infl uence how things are connected inside mitotic chromosomes, " explains Earn-shaw. " If you don't have these proteins, the chromosomes look almost normal, but things aren't hooked up properly inside. " Whereas KIF4 and condensin both compact mitotic chromosomes laterally, topo II␣ controls an opposing pathway that shortens chromosome arms. " If you don't have condensin or KIF4, the chromosomes are fatter and shorter, " says Same-jima, " but, if you deplete topo II␣, the chromosomes become thinner and longer. " To investigate the relationship between all three proteins, Samejima et al. depleted them in different combinations. " If you deplete KIF4 and condensin, the phenotype becomes much …