DOI: 10.1101/455873May 5, 2019Paper

Error correction is driven by direct competition between microtubules for interaction with a kinetochore

BioRxiv : the Preprint Server for Biology
Harinath DoodhiTomoyuki U Tanaka


For proper chromosome segregation, sister kinetochores must interact with microtubules from opposite spindle poles; this is called bi-orientation. To establish bi-orientation prior to chromosome segregation, any aberrant kinetochore-microtubule interaction must be resolved (error correction) by Aurora B kinase that phosphorylates outer kinetochore components. Aurora B differentially regulates kinetochore attachment to the microtubule plus end and its lateral side (end-on and lateral attachment). However, it is still unknown how kinetochore-microtubule interaction is turned over during error correction. Here we reconstituted the kinetochore-microtubule interface of budding yeast in vitro by attaching Ndc80 protein complexes (Ndc80Cs) to a nanobead that mimics the inner kinetochore. The Ndc80C-nanobeads recapitulated in vitro the lateral and end-on attachments of authentic kinetochores on dynamic microtubules loaded with the Dam1 complex. Using this system, we provide evidence that error correction is driven by direct competition for a kinetochore between the end-on attachment to one microtubule and the lateral attachment to another. We validated this competition-based error correction, using mathematical modelling and live-cell ...Continue Reading

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