Aurora B potentiates Mps1 activation to ensure rapid checkpoint establishment at the onset of mitosis

Adrian T. Saurin, Maike S. van der Waal, Rene H. Medema, Susanne M. A. Lens, Geert J. P. L. Kops

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    Abstract

    The mitotic checkpoint prevents mitotic exit until all chromosomes are attached to spindle microtubules. Aurora B kinase indirectly invokes this checkpoint by destabilizing incorrect attachments; however, a more direct role remains controversial. In contrast, activity of the kinase Mps1 is indispensible for the mitotic checkpoint. Here we show that Aurora B and Hec1 are needed for efficient Mps1 recruitment to unattached kinetochores, allowing rapid Mps1 activation at the onset of mitosis. Live monitoring of cyclin B degradation reveals that this is essential to establish the mitotic checkpoint quickly at the start of mitosis. Delayed Mps1 activation and checkpoint establishment upon Aurora B inhibition or Hec1 depletion are rescued by tethering Mps1 to kinetochores, demonstrating that Mps1 recruitment is the primary role of Aurora B and Hec1 in mitotic checkpoint signalling. These data demonstrate a direct role for Aurora B in initiating the mitotic checkpoint rapidly at the onset of mitosis.

    Original languageEnglish
    Article numberARTN 316
    Number of pages9
    JournalNature Communications
    Volume2
    DOIs
    Publication statusPublished - May 2011

    Keywords

    • CHROMOSOMAL PASSENGER COMPLEX
    • MAD2
    • MITOTIC CHECKPOINT
    • SPINDLE-ASSEMBLY CHECKPOINT
    • ANAPHASE-PROMOTING COMPLEX/CYCLOSOME
    • UNATTACHED KINETOCHORES
    • DYNAMICS
    • KINASE
    • CENP-E
    • KINETOCHORE-MICROTUBULE ATTACHMENT

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