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The anaphase promoting complex/cyclosome is recruited to centromeres by the spindle assembly checkpoint

Nature Cell Biology volume 6, pages 892–898 (2004)Cite this article

A Corrigendum to this article was published on 01 October 2004

Abstract

The anaphase promoting complex/cyclosome (APC/C) is crucial to the control of cell division (for a review, see ref. 1). It is a multi-subunit ubiquitin ligase that, at defined points during mitosis, targets specific proteins for proteasomal degradation. The APC/C is itself regulated by the spindle or kinetochore checkpoint, which has an important role in maintaining genomic stability by preventing sister chromatid separation until all chromosomes are correctly aligned on the mitotic spindle. The spindle checkpoint regulates the APC/C by inactivating Cdc20, an important co-activator of the APC/C. There is also evidence to indicate that the spindle checkpoint components and Cdc20 are spatially regulated by the mitotic apparatus, in particular they are recruited to improperly attached kinetochores. Here, we show that the APC/C itself co-localizes with components of the spindle checkpoint to improperly attached kinetochores. Indeed, we provide evidence that the spindle checkpoint machinery is required to recruit the APC/C to kinetochores. Our data indicate that the APC/C could be regulated directly by the spindle checkpoint.

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Figure 1: Dynamic localization of the APC/C during mitosis.
Figure 2: Order of assembly of Aurora B, APC3, Cdc20, Bub1 and BubR1 on the centromeres during prophase in HeLa cells.
Figure 3: Taxol and nocodazole induce the recruitment of APC/C to centromeres.
Figure 4: Centromeric localization of the APC/C is dependent on the activity of the spindle assembly checkpoint.
Figure 5: Aurora kinase activity is required for APC/C to be recruited to centromeres.

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Acknowledgements

We are grateful to N. Keen for the Aurora inhibitors; to T. Lorca for communicating results before publication; to J.-M. Peters for his generosity; to H. Vodermaier for valuable reagents and discussions; to A. Sossick for help with deconvolution; to B. Earnshaw, T. Salmon, J.-M. Peters and our colleagues in the laboratory for discussions; and to A. Hagting, C. Lindon, L. Clay and R. Basto for comments on the manuscript. C.A. was supported by an EU TMR network grant (contract number QLG1-CT-2001-02026), and the research was funded by Programme Grant C29/A1782 to J.P. from Cancer Research UK.

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  1. Wellcome Trust/Cancer Research UK Gurdon Institute and Department of Zoology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QR, UK

    Claire Acquaviva & Jonathon Pines

  2. Institute of Molecular Pathology, Dr Bohr Gasse, Vienna, Austria

    Franz Herzog & Claudine Kraft

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Correspondence to Jonathon Pines.

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Acquaviva, C., Herzog, F., Kraft, C. et al. The anaphase promoting complex/cyclosome is recruited to centromeres by the spindle assembly checkpoint. Nat Cell Biol 6, 892–898 (2004). https://doi.org/10.1038/ncb1167

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