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DNA damage-induced apoptosis

Oncogene volume 23, pages 2797–2808 (2004)Cite this article

Abstract

Unicellular organisms respond to the presence of DNA lesions by activating cell cycle checkpoint and repair mechanisms, while multicellular animals have acquired the further option of eliminating damaged cells by triggering apoptosis. Defects in DNA damage-induced apoptosis contribute to tumorigenesis and to the resistance of cancer cells to a variety of therapeutic agents. The intranuclear mechanisms that signal apoptosis after DNA damage overlap with those that initiate cell cycle arrest and DNA repair, and the early events in these pathways are highly conserved. In addition, multiple independent routes have recently been traced by which nuclear DNA damage can be signalled to the mitochondria, tipping the balance in favour of cell death rather than repair and survival. Here, we review current knowledge of nuclear DNA damage signalling, giving particular attention to interactions between these nuclear events and apoptotic processes in other intracellular compartments.

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Acknowledgements

We apologize to those authors whose work could not be cited directly due to space limitations. The work in our laboratories was supported by grants from Cancer Research UK, the Medical Research Council and the Association for International Cancer Research (to CJN), and from the Swedish (3829-B02-07XBC) and Stockholm (03:173) Cancer Societies, and EC grant (QLK3-CT-2002-01956) (to BZ).

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  1. Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford, OX1 3RE, UK

    Chris J Norbury

  2. Institute of Environmental Medicine, Karolinska Institutet, Box 210, Nobels väg. 13, Stockholm, SE-171 77, Sweden

    Boris Zhivotovsky

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Norbury, C., Zhivotovsky, B. DNA damage-induced apoptosis. Oncogene 23, 2797–2808 (2004). https://doi.org/10.1038/sj.onc.1207532

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