More than 100 proteins collaborate to build the kinetochore. Using RNAi, Liu et al. (page 41) sort out the responsibilities of key proteins in this process.
The kinetochore is a three-layered disc that sits on either side of the centromere. It links to spindle fibers and helps align and separate mitotic chromosomes. Although researchers have teased out the roles of some kinetochore proteins, they lacked a comprehensive picture of how these molecules interact to assemble the structure.
Liu et al. picked 20 putative kinetochore big shots and knocked them down, one at a time, using RNAi. The team then merged its results with past findings to sketch a map of the connections. Sitting atop the protein hierarchy is CENP-A, which permanently resides on centromeres. At the next level, three branches split off: two are headed by other centromere fixtures, CENP-I and CENP-C, and the third under the direction of the Aurora B kinase, a passenger protein crucial for chromosome separation.
Each branch takes on a different task. CENP-I establishes the three-layered organization, for example. Multiple cross-links tie the branches together, however, so there is no linear chain of command. The researchers are now investigating whether interacting proteins make direct contact or whether other molecules serve as intermediaries. The interaction map might be useful to pharmaceutical researchers developing anticancer drugs that disrupt kinetochore proteins. The map may point the way to biomarkers for monitoring the drugs' effects.