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Signalling dynamics in the spindle checkpoint response

Journal

NATURE REVIEWS MOLECULAR CELL BIOLOGY
Volume 15, Issue 11, Pages 735-747

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/nrm3888

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Funding

  1. US National Institutes of Health (NIH) centre interdisciplinary training grant [T32 CA080416]
  2. NIH [GM064386, GM078069]

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The spindle checkpoint ensures proper chromosome segregation during cell division. Unravelling checkpoint signalling has been a long-standing challenge owing to the complexity of the structures and forces that regulate chromosome segregation. New reports have now substantially advanced our understanding of checkpoint signalling mechanisms at the kinetochore, the structure that connects microtubules and chromatin. In contrast to the traditional view of a binary checkpoint response-either completely on or off-new findings indicate that the checkpoint response strength is variable. This revised perspective provides insight into how checkpoint bypass can lead to aneuploidy and informs strategies to exploit these errors for cancer treatments.

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