Chromosome congression by CENP-E and CENP-Q dependent pathways

Doctoral thesis English OPEN
Bancroft, James M.
  • Subject: QH
    mesheuropmc: health care economics and organizations | macromolecular substances

The timely and efficient movement of chromosomes to the spindle equator during mitosis is a prerequisite for accurate chromosome segregation. Recent work has shown that the majority of chromosomes are able to congress and biorientate almost instantaneously after nuclear envelope breakdown due to their position relative to the forming spindle. However, other mechanisms are required to facilitate the congression of chromosomes, which do not congress in this initial wave. Congression of these remaining chromosomes is mediated by multiple mechanisms including: (1) Kinetochore sliding along the microtubule lattice using the Kinesin-7 CENP-E, and (2) kinetochores biorientating near the pole and congressing through microtubule depolymerisation-coupled movement. Here, we show that the constitutive centromere associated network (CCAN) subunit CENP-Q is required for both mechanisms. CENP-Q is required to recruit CENP-E to kinetochores thus explaining the absence of lateral sliding in CENP-Q depleted cells. Because depletion or inhibition of the CENP-E motor does not affect depolymerisation-coupled pulling, we identify a CENP-E recruitment-independent role for CENP-Q in chromosome congression. Following congression we find that biorientated kinetochore movements require both CENP-Q and CENP-E dependent mechanisms. This suggests that as biorientated kinetochores congress they switch into a mode that requires CENP-E motor activity.
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