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For proper chromosome segregation, sister kinetochores must interact with microtubules from opposite spindle poles (bi-orientation). To establish bi-orientation, aberrant kinetochore-microtubule attachments are disrupted (error correction) by aurora B kinase (Ipl1 in budding yeast). Paradoxically, during this disruption, new attachments are still formed efficiently to enable fresh attempts at bi-orientation. How this is possible remains an enigma. Here we show that kinetochore attachment to the microtubule lattice (lateral attachment) is impervious to aurora B regulation, but attachment to the microtubule plus end (end-on attachment) is disrupted by this kinase. Thus, a new lateral attachment is formed without interference, then converted to end-on attachment and released if incorrect. This process continues until bi-orientation is established and stabilized by tension across sister kinetochores. We reveal how aurora B specifically promotes disruption of the end-on attachment through phospho-regulation of kinetochore components Dam1 and Ndc80. Our results reveal fundamental mechanisms for promoting error correction for bi-orientation.

Original publication

DOI

10.1038/ncb3128

Type

Journal article

Journal

Nat Cell Biol

Publication Date

04/2015

Volume

17

Pages

421 - 433

Keywords

Aurora Kinases, Binding Sites, Cell Cycle Proteins, Chromosome Segregation, Kinetochores, Microtubule-Associated Proteins, Microtubules, Mitosis, Mutation, Nuclear Proteins, Protein Binding, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Spindle Apparatus