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A mechanism for chromosome segregation sensing by the NoCut checkpoint

Nature Cell Biology volume 11, pages 477–483 (2009)Cite this article

Abstract

In Saccharomyces cerevisiae1 and HeLa cells2, the NoCut checkpoint, which involves the chromosome passenger kinase Aurora B, delays the completion of cytokinesis in response to anaphase defects. However, how NoCut monitors anaphase progression has not been clear. Here, we show that retention of chromatin in the plane of cleavage is sufficient to trigger NoCut, provided that Aurora/Ipl1 localizes properly to the spindle midzone, and that the ADA histone acetyltransferase complex is intact. Furthermore, forcing Aurora onto chromatin was sufficient to activate NoCut independently of anaphase defects. These findings provide the first evidence that NoCut is triggered by the interaction of acetylated chromatin with the passenger complex at the spindle midzone.

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Figure 1: Defects in chromosome segregation trigger NoCut-dependent inhibition of cytokinesis in the absence of midzone damage.
Figure 2: Separase is required for the NoCut response.
Figure 3: FEAR is required for the NoCut response through Ipl1 targeting to spindle microtubules.
Figure 4: The ADA histone acetyltransferase component Ahc1 is required for the NoCut response.
Figure 5: Tethering of Ipl1 to chromosome arms triggers the NoCut response.

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Acknowledgements

We are grateful to Patrick Steigemann, Daniel Gerlich, Patrick Meraldi, Hemmo Meyer and all members of the Barral lab for fruitful discussions and critical reading of the manuscript. Thanks to Dominik Theler, Trinidad Sanmartin and Joelle Sasse for technical assistance, Orna Cohen-Fix for sharing reagents, and the ETH Light Microscopy Center for their invaluable support. This work was supported by an SNF Grant to Y.B. (2-77542-04).

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Author notes

  1. Caren Norden

    Present address: Physiology Development and Neuroscience, Cambridge University, Downing St, CB2 3DY, Cambridge, UK

  2. Manuel Mendoza

    Present address: Current addresses: Centre for Genomic Regulation (CRG), C/ Dr. Aiguader, 88, 08003 Barcelona, Spain;,

Authors and Affiliations

  1. Biology Department, Institute of Biochemistry, ETH Zurich, 8093, Zurich, Switzerland

    Manuel Mendoza, Caren Norden, Kathrin Durrer, Harald Rauter & Yves Barral

  2. Chromosome Segregation Laboratory, Cancer Research UK London Research Institute, Lincoln's Inn Fields Laboratories, 44 Lincoln's Inn Fields, WC2A 3PX, London, United Kingdom

    Frank Uhlmann

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Correspondence to Yves Barral.

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Mendoza, M., Norden, C., Durrer, K. et al. A mechanism for chromosome segregation sensing by the NoCut checkpoint. Nat Cell Biol 11, 477–483 (2009). https://doi.org/10.1038/ncb1855

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