Aurora A kinase activity is required to maintain an active spindle assembly checkpoint during prometaphase

Abstract : During the prometaphase stage of mitosis, the cell builds a bipolar spindle of microtubules that mechanically segregates sister chromatids between two daughter cells in anaphase. The spindle assembly checkpoint (SAC) is a quality control mechanism that monitors proper attachment of microtubules to chromosome kinetochores during prometaphase. Segregation occurs only when each chromosome is bi-oriented with each kinetochore pair attached to microtubules emanating from opposite spindle poles. Overexpression of the protein kinase Aurora A is a feature of various cancers and is thought to enable tumour cells to bypass the SAC, leading to aneuploidy. Here, we took advantage of a chemical and chemical-genetic approach to specifically inhibit Aurora A kinase activity in late prometaphase. We observed that a loss of Aurora A activity directly affects SAC function, that Aurora A is essential for maintaining the checkpoint protein Mad2 on unattached kinetochores and that inhibition of Aurora A leads to loss of the SAC, even in the presence of nocodazole or Taxol. This is a new finding that should affect the way Aurora A inhibitors are used in cancer treatments.This article has an associated First Person interview with the first authors of the paper.
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Thibault Courtheoux, Alghassimou Diallo, Arun Prasath Damodaran, David Reboutier, Erwan Watrin, et al.. Aurora A kinase activity is required to maintain an active spindle assembly checkpoint during prometaphase. Journal of Cell Science, Company of Biologists, 2018, 131 (7), pp.jcs191353. ⟨10.1242/jcs.191353⟩. ⟨hal-01780367v2⟩

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