title: Adaptive changes in the kinetochore architecture facilitate proper spindle assembly.
abstract: Mitotic spindle formation relies on the stochastic capture of microtubules at kinetochores. Kinetochore architecture affects the efficiency and fidelity of this process with large kinetochores expected to accelerate assembly at the expense of accuracy, and smaller kinetochores to suppress errors at the expense of efficiency. We demonstrate that on mitotic entry, kinetochores in cultured human cells form large crescents that subsequently compact into discrete structures on opposite sides of the centromere. This compaction occurs only after the formation of end-on microtubule attachments. Live-cell microscopy reveals that centromere rotation mediated by lateral kinetochore-microtubule interactions precedes the formation of end-on attachments and kinetochore compaction. Computational analyses of kinetochore expansion-compaction in the context of lateral interactions correctly predict experimentally observed spindle assembly times with reasonable error rates. The computational model suggests that larger kinetochores reduce both errors and assembly times, which can explain the robustness of spindle assembly and the functional significance of enlarged kinetochores.
authors.affiliation: Wadsworth Center, New York State Department of Health, Albany, New York 12201, USA.
authors.forename: Valentin
authors.initials: V
authors.lastname: Magidson
authors.affiliation: Indian Association for the Cultivation of Science, Jadavpur, Kolkata 700032, India.|Courant Institute and Department of Biology, New York University, New York, New York 10012, USA.
authors.forename: Raja
authors.initials: R
authors.lastname: Paul
authors.affiliation: Wadsworth Center, New York State Department of Health, Albany, New York 12201, USA.
authors.forename: Nachen
authors.initials: N
authors.lastname: Yang
authors.affiliation: Wadsworth Center, New York State Department of Health, Albany, New York 12201, USA.
authors.forename: Jeffrey G
authors.initials: JG
authors.lastname: Ault
authors.affiliation: Wadsworth Center, New York State Department of Health, Albany, New York 12201, USA.
authors.forename: Christopher B
authors.initials: CB
authors.lastname: O'Connell
authors.affiliation: Wadsworth Center, New York State Department of Health, Albany, New York 12201, USA.
authors.forename: Irina
authors.initials: I
authors.lastname: Tikhonenko
authors.affiliation: Wadsworth Center, New York State Department of Health, Albany, New York 12201, USA.
authors.forename: Bruce F
authors.initials: BF
authors.lastname: McEwen
authors.affiliation: Courant Institute and Department of Biology, New York University, New York, New York 10012, USA.
authors.forename: Alex
authors.initials: A
authors.lastname: Mogilner
authors.affiliation: Wadsworth Center, New York State Department of Health, Albany, New York 12201, USA.|Rensselaer Polytechnic Institute, Troy, New York 12180, USA.
authors.forename: Alexey
authors.initials: A
authors.lastname: Khodjakov
mesh_terms: D002460:Cell Line; D002877:Chromosomes, Human / Q000378:metabolism; D006801:Humans; D018386:Kinetochores / Q000378:metabolism / Q000648:ultrastructure*; D059566:M Phase Cell Cycle Checkpoints; D008870:Microtubules / Q000378:metabolism; D021381:Protein Transport; D008941:Spindle Apparatus / Q000378:metabolism*