Abstract
To establish chromosome biorientation, aberrant kinetochore-microtubule interaction must be resolved (error correction) by Aurora B kinase. Aurora B differentially regulates kinetochore attachment to the microtubule plus end and its lateral side (end-on and lateral attachment, respectively). However, it is still unclear how kinetochore-microtubule interactions are exchanged during error correction. Here, we reconstituted the budding yeast kinetochore-microtubule interface in vitro by attaching the Ndc80 complexes to nanobeads. These Ndc80C nanobeads recapitulated in vitro the lateral and end-on attachments of authentic kinetochores on dynamic microtubules loaded with the Dam1 complex. This in vitro assay enabled the direct comparison of lateral and end-on attachment strength and showed that Dam1 phosphorylation by Aurora B makes the end-on attachment weaker than the lateral attachment. Similar reconstitutions with purified kinetochore particles were used for comparison. We suggest the Dam1 phosphorylation weakens interaction with the Ndc80 complex, disrupts the end-on attachment, and promotes the exchange to a new lateral attachment, leading to error correction.
Highlights
For accurate and successful chromosome segregation, kineto- A, steps 1 and 2) and subsequently replaced by lateral attachchores must interact properly with spindle microtubules ment to a different MT; the lateral attachment is (MTs; Tanaka, 2010)
For exchange to occur efficiently, an end-on attachment to one MT must be disrupted and replaced by a lateral attachment to another MT. It is unknown how the relative strengths of lateral ened by the action of Aurora B, but the lateral attachment is impervious to Aurora B regulation
This led us to propose the model that during error correction, an end-on attachment is disrupted by the action of Aurora B
Summary
For accurate and successful chromosome segregation, kineto- A, steps 1 and 2) and subsequently replaced by lateral attachchores must interact properly with spindle microtubules ment to a different MT (steps 3 and 4); the lateral attachment is (MTs; Tanaka, 2010). Sister kinetochores form end-on attachments to MTs extending from opposite spindle poles, establishing chromosome biorientation. If an aberrant kinetochore–MT attachment is formed, it must be resolved (error correction) by Aurora B kinase (Ipl in budding yeast), which phosphorylates kinetochore components and disrupts the end-on attachment (Hauf et al, 2003; Lampson et al, 2004; Tanaka et al, 2002). The model suggests that differential regulation of end-on and lateral attachments promotes the exchange of kinetochore–MT interactions for error correction
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
