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The Nucleoshuttling of the ATM Protein: A Unified Model to Describe the Individual Response to High- and Low-Dose of Radiation?

Institut National de la Santé et de la Recherche Médicale, UA8, Radiations: Defense, Health and Environment, Centre Léon-Bérard, 28, rue Laennec, 69008 Lyon, France
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Cancers 2019, 11(7), 905; https://doi.org/10.3390/cancers11070905
Received: 21 May 2019 / Revised: 22 June 2019 / Accepted: 25 June 2019 / Published: 28 June 2019
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Abstract

The evaluation of radiation-induced (RI) risks is of medical, scientific, and societal interest. However, despite considerable efforts, there is neither consensual mechanistic models nor predictive assays for describing the three major RI effects, namely radiosensitivity, radiosusceptibility, and radiodegeneration. Interestingly, the ataxia telangiectasia mutated (ATM) protein is a major stress response factor involved in the DNA repair and signaling that appears upstream most of pathways involved in the three precited RI effects. The rate of the RI ATM nucleoshuttling (RIANS) was shown to be a good predictor of radiosensitivity. In the frame of the RIANS model, irradiation triggers the monomerization of cytoplasmic ATM dimers, which allows ATM monomers to diffuse in nucleus. The nuclear ATM monomers phosphorylate the H2AX histones, which triggers the recognition of DNA double-strand breaks and their repair. The RIANS model has made it possible to define three subgroups of radiosensitivity and provided a relevant explanation for the radiosensitivity observed in syndromes caused by mutated cytoplasmic proteins. Interestingly, hyper-radiosensitivity to a low dose and adaptive response phenomena may be also explained by the RIANS model. In this review, the relevance of the RIANS model to describe several features of the individual response to radiation was discussed. View Full-Text
Keywords: radiosensitivity; ATM; DSB repair radiosensitivity; ATM; DSB repair
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Berthel, E.; Foray, N.; Ferlazzo, M.L. The Nucleoshuttling of the ATM Protein: A Unified Model to Describe the Individual Response to High- and Low-Dose of Radiation? Cancers 2019, 11, 905.

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