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

TY - JOUR

T1 - Aurora B potentiates Mps1 activation to ensure rapid checkpoint establishment at the onset of mitosis

AU - Saurin, Adrian T.

AU - van der Waal, Maike S.

AU - Medema, Rene H.

AU - Lens, Susanne M. A.

AU - Kops, Geert J. P. L.

PY - 2011/5

Y1 - 2011/5

N2 - 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.

AB - 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.

KW - CHROMOSOMAL PASSENGER COMPLEX

KW - MAD2

KW - MITOTIC CHECKPOINT

KW - SPINDLE-ASSEMBLY CHECKPOINT

KW - ANAPHASE-PROMOTING COMPLEX/CYCLOSOME

KW - UNATTACHED KINETOCHORES

KW - DYNAMICS

KW - KINASE

KW - CENP-E

KW - KINETOCHORE-MICROTUBULE ATTACHMENT

UR - https://www.scopus.com/pages/publications/79956266042

U2 - 10.1038/ncomms1319

DO - 10.1038/ncomms1319

M3 - Article

C2 - 21587233

SN - 2041-1723

VL - 2

JO - Nature Communications

JF - Nature Communications

M1 - ARTN 316

ER -