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Flies without a spindle checkpoint

Abstract

Mad2 has a key role in the spindle-assembly checkpoint (SAC) — the mechanism delaying anaphase onset until all chromosomes correctly attach to the spindle. Here, we show that unlike every other reported case of SAC inactivation in metazoans, mad2-null Drosophila are viable and fertile, and their cells almost always divide correctly despite having no SAC and an accelerated 'clock', which is caused by premature degradation of cyclin B. Mitosis in Drosophila does not need the SAC because correct chromosome attachment is achieved very rapidly, before even the cell lacking Mad2 can initiate anaphase. Experimentally reducing spindle-assembly efficiency renders the cells Mad2-dependent. In fact, the robustness of the SAC may generally mask minor mitotic defects of mutations affecting spindle function. The reported lethality of other Drosophila SAC mutations may be explained by their multifunctionality, and thus the 'checkpoint' phenotypes previously ascribed to these mutations should be considered the consequence of eliminating both the checkpoint and a second mitotic function.

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Figure 1: Drosophila mitosis is normal in the absence of Mad2.
Figure 2: Anaphase onset is accelerated in mad2 mutant neuroblasts.
Figure 3: OCBD is accelerated in mad2-mutant neuroblasts.

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Acknowledgements

We thank: J. Montagne and D. Pauli for stocks of Ds6k and noisette aberrations, respectively; J. Raff for GFP–cyclin B flies; G. Rogers for his unpublished Mad2 antibody; and H. Quesneville and M.-H. Mucchielli for help with statistics. This work was supported by grants from the Centre National de la Recherche Scientifique (CNRS) to R.K., the Association pour la Recherche sur le Cancer (ARC) to R.K. and E.B., La Ligue Nationale Contre le Cancer to R.K., and Le Ministère de l'Education Nationale de la Recherche et de la Technologie to E.B. and D.E.

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Buffin, E., Emre, D. & Karess, R. Flies without a spindle checkpoint. Nat Cell Biol 9, 565–572 (2007). https://doi.org/10.1038/ncb1570

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