Complications Dawn for Kinetochore Regulation by Aurora

Abstract

Organisms must faithfully segregate their chromosomes during cell division; mistakes in this process can be costly and even fatal to the organism (1, 2). During mitosis, replicated chromosomes attach to the spindle, a dynamic system of microtubules organized around two poles. Chromosomes attach to the spindle via kinetochores, structures that form on centromeres and bind the ends of microtubules. For accurate segregation, kinetochores on sister chromosomes must attach to microtubules from opposite poles; incorrect attachments lead to missegregation (3). In PNAS, Umbreit et al. (4) expand our understanding of how kinetochore–microtubule interactions can be regulated to correct improper attachments. The authors use in vitro studies to demonstrate that a component of the kinetochore, the Ndc80 complex, can directly influence the dynamics of the microtubules it is bound to and how the complex can be regulated to correct errors in chromosome attachment. Kinetochores are complicated machines. They can stay attached to microtubule ends as they grow and shrink, regulate the dynamics of microtubules, regulate their own activity, and signal to the remainder of the cell. The outer layer of the kinetochore contains the dumbbell-shaped Ndc80 complex (5): One globular domain [the N-terminal domains of Hec1 (Ndc80 in budding yeast) and Nuf2] binds microtubules (6) and is connected by a long coiled coil to the other globular domain (composed of the C-terminal domains of Spc24/Spc25), which connects to other kinetochore components (7) (Fig. 1A). Hec1 contains a conserved calponin homology domain and an unstructured N-terminal tail: Both regions can bind to microtubules independently, but they must act together to produce high-affinity binding (5⇓⇓–8). When sister kinetochores attach...(see full text).