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

  • Atsushi Shibata
  • Penny JeggoEmail author
Part of the Cancer Drug Discovery and Development book series (CDD&D)


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.


DNA damage signalling Radiosensitivity DNA double-strand break repair Cell cycle checkpoints Apoptosis Ataxia telangiectasia 


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© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Eduction and Research Support Centre, Graduate School of MedicineGunma UniversityMaebashiJapan
  2. 2.Genome Damage and Stability Centre, Life SciencesUniversity of SussexBrightonUK

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