4.8 Article

Evidence that Aurora B is implicated in spindle checkpoint signalling independently of error correction

Journal

EMBO JOURNAL
Volume 30, Issue 8, Pages 1508-1519

Publisher

WILEY
DOI: 10.1038/emboj.2011.70

Keywords

centromere; hesperadin; kinetochore; reversine; tension

Funding

  1. Association for International Cancer Research (AICR)
  2. Telethon Foundation
  3. European Research Council [241548]
  4. Italian Association for Cancer Research (AIRC)
  5. Fondo di Investimento per la Ricerca di Base (FIRB)
  6. Cariplo Foundation
  7. Human Frontier Science Program
  8. Italian Foundation for Cancer Research (FIRC).

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Fidelity of chromosome segregation is ensured by a tension-dependent error correction system that prevents stabilization of incorrect chromosome-microtubule attachments. Unattached or incorrectly attached chromosomes also activate the spindle assembly checkpoint, thus delaying mitotic exit until all chromosomes are bioriented. The Aurora B kinase is widely recognized as a component of error correction. Conversely, its role in the checkpoint is controversial. Here, we report an analysis of the role of Aurora B in the spindle checkpoint under conditions believed to uncouple the effects of Aurora B inhibition on the checkpoint from those on error correction. Partial inhibition of several checkpoint and kinetochore components, including Mps1 and Ndc80, strongly synergizes with inhibition of Aurora B activity and dramatically affects the ability of cells to arrest in mitosis in the presence of spindle poisons. Thus, Aurora B might contribute to spindle checkpoint signalling independently of error correction. Our results support a model in which Aurora B is at the apex of a signalling pyramid whose sensory apparatus promotes the concomitant activation of error correction and checkpoint signalling pathways. The EMBO Journal (2011) 30, 1508-1519. doi:10.1038/emboj.2011.70; Published online 15 March 2011 Subject Categories: cell cycle

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