Kalantzaki Maria, Kitamura Etsushi, Zhang Tongli, Mino Akihisa, Novák Béla, Tanaka Tomoyuki U
Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee, Dow Street Dundee DD1 5EH, UK.
Oxford Centre for Integrative Systems Biology, Department of Biochemistry, University of Oxford, South Parks Road Oxford OX1 3QU, UK.
Nat Cell Biol. 2015 Apr;17(4):421-33. doi: 10.1038/ncb3128. Epub 2015 Mar 9.
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.
为实现正确的染色体分离，姐妹动粒必须与来自纺锤体两极相对的微管相互作用（双极定向）。为建立双极定向，异常的动粒-微管附着会被极光B激酶（芽殖酵母中的Ipl1）破坏（错误校正）。矛盾的是，在这种破坏过程中，新的附着仍能高效形成，以便重新尝试双极定向。这是如何实现的仍是一个谜。在这里，我们表明动粒与微管晶格的附着（侧向附着）不受极光B调控的影响，但与微管正端的附着（端对端附着）会被这种激酶破坏。因此，新的侧向附着不受干扰地形成，然后转换为端对端附着，如果不正确则会被释放。这个过程持续进行，直到通过姐妹动粒间的张力建立并稳定双极定向。我们揭示了极光B如何通过对动粒组分Dam1和Ndc80的磷酸化调节来特异性地促进端对端附着的破坏。我们的结果揭示了促进双极定向错误校正的基本机制。
