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Mitotic errors as triggers of cell death and inflammation

Nature Cell Biology volume 28, pages 21–34 (2026)Cite this article

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Abstract

Bursts of cell proliferation after infection, injury or transformation can coincide with DNA damage and spindle assembly defects. These increase the risk of cell cycle arrest in mitosis, during which many cellular processes are uniquely regulated. Ultimately, cells arrested during mitosis may die, but adaptive mechanisms also allow their escape into the next interphase. This step can have variable consequences, including chromosome missegregation, polyploidization and centrosome amplification. Escaping cells can also initiate innate immune signalling, enter senescence or engage cell death, which in turn alert the microenvironment through nucleic acid sensing mechanisms and/or the release of danger-associated molecular patterns. Here we discuss the causes and consequences of deregulated mitosis and postmitotic cell fate, highlighting the impact of DNA damage repair, the spindle assembly checkpoint and extra centrosomes on genome integrity, as well as inflammatory signalling. Finally, we attempt to reconcile conflicting observations and propose variable modes that activate innate immune responses after mitotic perturbations.

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Fig. 1: Unique features of mitosis and possible consequences of mitotic errors.
Fig. 2: Initiation and execution of mitotic cell death.
Fig. 3: Possible consequences of mitotic escape.
Fig. 4: Possible sources of inflammation in response to mitotic errors.

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Acknowledgements

A.V. acknowledges support by the Austrian Science Fund (FWF) (10.55776/I6642, TRR353 and 10.55776/FG25) and the European Research Council (ERC AdG POLICE #787171). C.Z. acknowledges support from Cancer Research UK (RCCFEL\100092), the Cancer Research UK Radiation Research Centre of Excellence at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust (A28724 and RRCOER-Jun24/100006) and Breast Cancer Now (2023.05PR1625). We also thank N. Kinz and M. Schapfl for help with preparing the figures.

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  1. These authors contributed equally: Dario Rizzotto, Christian Zierhut, Andreas Villunger.

Authors and Affiliations

  1. CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria

    Dario Rizzotto & Andreas Villunger

  2. Division of Cell and Molecular Biology, The Institute of Cancer Research, London, UK

    Christian Zierhut

  3. Institute for Developmental Immunology, Biocenter, Medical University of Innsbruck, Innsbruck, Austria

    Andreas Villunger

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  2. Christian Zierhut
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All authors contributed equally. D.R., C.Z. and A.V. led the reviewing and writing of individual sections that were subsequently cross-checked and edited by each author. C.Z. developed Fig. 1, A.V. developed Figs. 2–4. All figures were edited by D.R., C.Z. and A.V.

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Rizzotto, D., Zierhut, C. & Villunger, A. Mitotic errors as triggers of cell death and inflammation. Nat Cell Biol 28, 21–34 (2026). https://doi.org/10.1038/s41556-025-01785-9

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