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Volume 16
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Caffeine May Delay the Radiation-Induced Nucleoshuttling of the ATM Kinase and Reduce the Recognition of the DNA Double-Strand Breaks in Human Cells

by
Léonie Moliard
1,
Juliette Restier-Verlet
1,
Joëlle Al-Choboq
1,
Adeline Granzotto
1,
Laurent Charlet
2,
Jacques Balosso
3,
Michel Bourguignon
1,4,
Laurent Pujo-Menjouet
5 and
Nicolas Foray
1,*
1
Institut National de la Santé et de la Recherche Médicale (INSERM) U1296 Unit “Radiation: Defense, Health, Environment”, 28 Rue Laennec, 69008 Lyon, France
2
Institute of Earth Science (ISTerre), Université Grenoble Alpes, Université Savoie Mont Blanc, Centre National de Recherche Scientifique (CNRS), Institut de Recherche pour le Développement (IRD), Université Gustave Eiffel, 38000 Grenoble, France
3
Service de Radiothérapie, Centre Hospitalo-Universitaire (CHU) de Grenoble, 38000 La Tronche, France
4
Université Paris Saclay, Université Versailles Saint-Quentin (UVSQ), 78180 Montigny le Bretonneux, France
5
Université Claude Bernard Lyon 1, Centre National de Recherche Scientifique (CNRS), Centrale Lyon, Institut National des Sciences Appliquées (INSA) Lyon, Université Jean Monnet, Institut Camille Jordan(ICJ) UMR5208, Institut National de Recherche en Sciences et Technologies du Numérique (INRIA), 69622 Villeurbanne, France
*
Author to whom correspondence should be addressed.
Biomolecules 2026, 16(1), 41; https://doi.org/10.3390/biom16010041
Submission received: 7 November 2025 / Revised: 18 December 2025 / Accepted: 22 December 2025 / Published: 25 December 2025
(This article belongs to the Section Natural and Bio-derived Molecules)
Review Reports Versions Notes

Abstract

Since 2014, a model of the individual response to ionizing radiation (IR), based on the radiation-induced nucleoshuttling of the ATM protein kinase (RIANS), has been developed by our lab: after irradiation, ATM dimers monomerize in cytoplasm and diffuse into the nucleus to trigger both recognition and repair of DNA double-strand breaks (DSB), the key-damage of IR response. Moderate radiosensitivity is generally caused by heterozygous mutations of ATM substrates (called X-proteins) that are over-expressed in cytoplasm and form complexes with ATM monomers, which reduces and/or delays the RIANS and DSB recognition. Here, we asked whether molecules, rather than X-proteins, can also influence RIANS. Caffeine was chosen as a potential “X-molecule” candidate. After incubation of cells with caffeine, cutaneous fibroblasts from an apparently healthy radioresistant donor, a patient suffering from Alzheimer’s disease (AD) and another suffering from neurofibromatosis type 1 (NF1) were exposed to X-rays. The functionality of ATM-dependent DSB repair and signaling was evaluated. We report here that caffeine molecule interaction with ATM leads to the inhibition of DSB recognition. This effect is significant in radioresistant cells. Conversely, in the AD and NF1 cells, the DSB recognition is already so low that caffeine does not provide any additional molecular effect.
Keywords: caffeine; radiation; ATM; DNA double-strand breaks; human fibroblast caffeine; radiation; ATM; DNA double-strand breaks; human fibroblast

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MDPI and ACS Style

Moliard, L.; Restier-Verlet, J.; Al-Choboq, J.; Granzotto, A.; Charlet, L.; Balosso, J.; Bourguignon, M.; Pujo-Menjouet, L.; Foray, N. Caffeine May Delay the Radiation-Induced Nucleoshuttling of the ATM Kinase and Reduce the Recognition of the DNA Double-Strand Breaks in Human Cells. Biomolecules 2026, 16, 41. https://doi.org/10.3390/biom16010041

AMA Style

Moliard L, Restier-Verlet J, Al-Choboq J, Granzotto A, Charlet L, Balosso J, Bourguignon M, Pujo-Menjouet L, Foray N. Caffeine May Delay the Radiation-Induced Nucleoshuttling of the ATM Kinase and Reduce the Recognition of the DNA Double-Strand Breaks in Human Cells. Biomolecules. 2026; 16(1):41. https://doi.org/10.3390/biom16010041

Chicago/Turabian Style

Moliard, Léonie, Juliette Restier-Verlet, Joëlle Al-Choboq, Adeline Granzotto, Laurent Charlet, Jacques Balosso, Michel Bourguignon, Laurent Pujo-Menjouet, and Nicolas Foray. 2026. "Caffeine May Delay the Radiation-Induced Nucleoshuttling of the ATM Kinase and Reduce the Recognition of the DNA Double-Strand Breaks in Human Cells" Biomolecules 16, no. 1: 41. https://doi.org/10.3390/biom16010041

APA Style

Moliard, L., Restier-Verlet, J., Al-Choboq, J., Granzotto, A., Charlet, L., Balosso, J., Bourguignon, M., Pujo-Menjouet, L., & Foray, N. (2026). Caffeine May Delay the Radiation-Induced Nucleoshuttling of the ATM Kinase and Reduce the Recognition of the DNA Double-Strand Breaks in Human Cells. Biomolecules, 16(1), 41. https://doi.org/10.3390/biom16010041

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