Lampert et al. show how two kinetochore protein complexes work together to link up with microtubules.
Kinetochores hitch spindle microtubules to the centromeres, helping ensure that chromosomes separate properly during mitosis. In yeast cells, two protein complexes—Ndc80 and Dam1—make the connection to microtubules. Ndc80 clings to the kinetochore, whereas Dam1 may form a ring around the microtubule. Although previous studies suggested that the two complexes cooperate, researchers didn’t understand how they interact.
Lampert et al. addressed this question by testing the effects of different Ndc80 mutations on yeast cells. The researchers found that mutations in the portion of Ndc80 that attaches to Dam1 slowed cell growth and disrupted chromosome segregation, suggesting that Ndc80 and Dam1 need to make contact to work properly. The cells perished if the team combined one of these mutations with a different defect that shaves off part of Ndc80’s N-terminal tail, indicating that the Dam1-binding site and N-terminal tail perform partly redundant functions.
The team also discovered that mutations in Ndc80’s calponin homology domain prevented kinetochores from latching onto microtubules and were fatal for the cells. Previous studies have found that Ndc80 is crucial for kinetochore–microtubule attachment in human cells, and the new results confirm that this function is conserved in yeast.
Text by Mitch Leslie