@article{907226606b55412d981abd80cbe1113b,
title = "Dynamic kinetochore size regulation promotes microtubule capture and chromosome biorientation in mitosis",
abstract = "Faithful chromosome segregation depends on the ability of sister kinetochores to attach to spindle microtubules. The outer layer of kinetochores transiently expands in early mitosis to form a fibrous corona, and compacts following microtubule capture. Here we show that the dynein adaptor Spindly and the RZZ (ROD-Zwilch-ZW10) complex drive kinetochore expansion in a dynein-independent manner. C-terminal farnesylation and MPS1 kinase activity cause conformational changes of Spindly that promote oligomerization of RZZ-Spindly complexes into a filamentous meshwork in cells and in vitro. Concurrent with kinetochore expansion, Spindly potentiates kinetochore compaction by recruiting dynein via three conserved short linear motifs. Expanded kinetochores unable to compact engage in extensive, long-lived lateral microtubule interactions that persist to metaphase, and result in merotelic attachments and chromosome segregation errors in anaphase. Thus, dynamic kinetochore size regulation in mitosis is coordinated by a single, Spindly-based mechanism that promotes initial microtubule capture and subsequent correct maturation of attachments.",
author = "Carlos Sacristan and Ahmad, \{Misbha Ud Din\} and Jenny Keller and Job Fermie and Vincent Groenewold and Eelco Tromer and Alexander Fish and Roberto Melero and Carazo, \{Jos{\'e} Mar{\'i}a\} and Judith Klumperman and Andrea Musacchio and Anastassis Perrakis and Kops, \{Geert Jpl\}",
note = "Funding Information: We thank all lab members for suggestions and discussions. We are grateful to A. Murachelli for help with EM data figure preparation; to E. von Castelmur, T. Heidebrecht and Y. Hiruma for help with Spindly structure experiments; to J. Vaughan for help with ExM; to R. Gassmann for sharing unpublished results and Spindly constructs; to I. Cheeseman, S. Lens and R. Medema for reagents; and to A. de Graaf of the Hubrecht Imaging Center. The Horizon 2020 iNEXT project (653706) provided financial support and access to EM infrastructures. This work is part of the Oncode Institute which is partly financed by the Dutch Cancer Society. This work was further supported by the Netherlands Organisation for Scientific Research (NWO) (gravitation program CancerGenomiCs.nl; VICI grant (865.12.004 to G.J.P.L.K.)), the Dutch Cancer Society (KWF/HUBR-11080 to G.J.P.L.K.), and the ERC (675737 to A.M.). V.G. is supported by the Proteins@Work initiative of the Netherlands Proteomics Centre. Publisher Copyright: {\textcopyright} 2018 The Author(s).",
year = "2018",
month = jul,
day = "1",
doi = "10.1038/s41556-018-0130-3",
language = "English",
volume = "20",
pages = "800--810",
journal = "Nature Cell Biology",
issn = "1465-7392",
publisher = "Nature Research",
number = "7",
}