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ATM: Its Recruitment, Activation, Signalling and Contribution to Tumour Suppression

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Targeting the DNA Damage Response for Anti-Cancer Therapy

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

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Abstract

DNA double strand breaks (DSBs) are a critical lesion for cancer etiology. Most cancer cells incur increased DNA breakage to enhance genomic instability. The DSB damage response encompasses pathways of repair and a signal transduction pathway. The ataxia telangiectasia mutated (ATM) kinase lies at the centre of the signalling response. ATM is not essential for the major DSB repair process in mammalian cells but influences DSB repair, including its accuracy, in multiple ways. ATM is activated by DSBs to promote cell cycle checkpoint arrest and apoptosis. There is mounting evidence that ATM is active endogenously and/or that it can be activated by non-DSB routes, including oxidative damage. It plays an important role in regulating cellular redox status. The tumour suppressor functions of ATM are discussed. Paradoxically, since elevated DSBs arise in cancer cells, despite being a tumour suppressor, pharmacological inhibition of ATM is a promising route for cancer therapy.

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Authors and Affiliations

  1. Eduction and Research Support Centre, Graduate School of Medicine, Gunma University, Maebashi, Gunma, Japan

    Atsushi Shibata

  2. Genome Damage and Stability Centre, Life Sciences, University of Sussex, Brighton, UK

    Penny Jeggo

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  1. Atsushi Shibata
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  2. Penny Jeggo
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Correspondence to Penny Jeggo .

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  1. Vertex Pharmaceuticals (Europe) Ltd, Abingdon, Oxfordshire, United Kingdom

    John Pollard

  2. Northern Institute for Cancer Research, Medical School, Newcastle University, Newcastle upon Tyne, United Kingdom

    Nicola Curtin

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Shibata, A., Jeggo, P. (2018). ATM: Its Recruitment, Activation, Signalling and Contribution to Tumour Suppression. In: Pollard, J., Curtin, N. (eds) Targeting the DNA Damage Response for Anti-Cancer Therapy. Cancer Drug Discovery and Development. Humana Press, Cham. https://doi.org/10.1007/978-3-319-75836-7_6

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  • DOI: https://doi.org/10.1007/978-3-319-75836-7_6

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  • Online ISBN: 978-3-319-75836-7

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