Using an in vitro assay for proteins that stimulate microtubule formation, the team isolated the human Shugoshin (Sgo) protein. Yeast and fly homologues are essential for mitosis and their loss is known to cause dramatic defects in sister centromere cohesion in meiosis.
In affinity purification experiments, human Sgo brings down tubulin, and the interaction appears to be direct. Sgo localizes to the kinetochore and is degraded by the anaphase-promoting complex before the cell exits mitosis.
Sgo siRNA causes mitotic arrest and failed centromere cohesion; single chromosomes are found scattered over the entire spindle. Any remaining paired kinetochores are closer than normal, indicating a lack of tension, and fluorescently marked kinetochore microtubules turn over much more rapidly. The double function of Sgo as a kinetochore–microtubule stabilizing protein and a cohesion protein is “an interesting twist, but not unbelievable,” says Salic. ▪