Kinetochore alignment within the metaphase plate is regulated by centromere stiffness and microtubule depolymerases

Khuloud Jaqaman, Emma M. King, Ana C. Amaro, Jennifer R. Winter, Jonas F. Dorn, Hunter L. Elliott, Nunu Mchedlishvili, Sarah E. McClelland, Iain M. Porter, Markus Posch, Alberto Toso, Gaudenz Danuser (Lead / Corresponding author), Andrew D. McAinsh (Lead / Corresponding author), Patrick Meraldi (Lead / Corresponding author), Jason R. Swedlow (Lead / Corresponding author)

    Research output: Contribution to journalArticlepeer-review

    94 Citations (Scopus)
    228 Downloads (Pure)

    Abstract

    During mitosis in most eukaryotic cells, chromosomes align and form a metaphase plate halfway between the spindle poles, about which they exhibit oscillatory movement. These movements are accompanied by changes in the distance between sister kinetochores, commonly referred to as breathing. We developed a live cell imaging assay combined with computational image analysis to quantify the properties and dynamics of sister kinetochores in three dimensions. We show that baseline oscillation and breathing speeds in late prometaphase and metaphase are set by microtubule depolymerases, whereas oscillation and breathing periods depend on the stiffness of the mechanical linkage between sisters. Metaphase plates become thinner as cells progress toward anaphase as a result of reduced oscillation speed at a relatively constant oscillation period. The progressive slowdown of oscillation speed and its coupling to plate thickness depend nonlinearly on the stiffness of the mechanical linkage between sisters. We propose that metaphase plate formation and thinning require tight control of the state of the mechanical linkage between sisters mediated by centromeric chromatin and cohesion.

    Original languageEnglish
    Pages (from-to)665-679
    Number of pages15
    JournalJournal of Cell Biology
    Volume188
    Issue number5
    DOIs
    Publication statusPublished - 8 Mar 2010

    Keywords

    • SPINDLE-ASSEMBLY CHECKPOINT
    • CHROMOSOME ALIGNMENT
    • MITOTIC CHROMOSOME
    • HUMAN-CELLS
    • CENP-E
    • MCAK
    • ANAPHASE
    • COHESIN
    • CONGRESSION
    • ATTACHMENT

    Cite this