{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T05:31:06Z","timestamp":1767072666408,"version":"3.48.0"},"reference-count":42,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,25]],"date-time":"2025-12-25T00:00:00Z","timestamp":1766620800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006072","name":"Commissariat G\u00e9n\u00e9ral \u00e0 l'Investissement","doi-asserted-by":"publisher","award":["INDIRA Project"],"award-info":[{"award-number":["INDIRA Project"]}],"id":[{"id":"10.13039\/501100006072","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006364","name":"Institut National du Cancer","doi-asserted-by":"publisher","award":["PROUST Project"],"award-info":[{"award-number":["PROUST Project"]}],"id":[{"id":"10.13039\/501100006364","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002830","name":"Centre National d'\u00c9tudes Spatiales","doi-asserted-by":"publisher","award":["ICARE Project"],"award-info":[{"award-number":["ICARE Project"]}],"id":[{"id":"10.13039\/501100002830","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["France 2030 SHAPEMED@Lyon MAHATMA Project"],"award-info":[{"award-number":["France 2030 SHAPEMED@Lyon MAHATMA Project"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>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 \u201cX-molecule\u201d candidate. After incubation of cells with caffeine, cutaneous fibroblasts from an apparently healthy radioresistant donor, a patient suffering from Alzheimer\u2019s 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.<\/jats:p>","DOI":"10.3390\/biom16010041","type":"journal-article","created":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T02:07:58Z","timestamp":1766714878000},"page":"41","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Caffeine May Delay the Radiation-Induced Nucleoshuttling of the ATM Kinase and Reduce the Recognition of the DNA Double-Strand Breaks in Human Cells"],"prefix":"10.3390","volume":"16","author":[{"given":"L\u00e9onie","family":"Moliard","sequence":"first","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM) U1296 Unit \u201cRadiation: Defense, Health, Environment\u201d, 28 Rue Laennec, 69008 Lyon, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juliette","family":"Restier-Verlet","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM) U1296 Unit \u201cRadiation: Defense, Health, Environment\u201d, 28 Rue Laennec, 69008 Lyon, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6772-6947","authenticated-orcid":false,"given":"Jo\u00eblle","family":"Al-Choboq","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM) U1296 Unit \u201cRadiation: Defense, Health, Environment\u201d, 28 Rue Laennec, 69008 Lyon, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adeline","family":"Granzotto","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM) U1296 Unit \u201cRadiation: Defense, Health, Environment\u201d, 28 Rue Laennec, 69008 Lyon, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3669-7316","authenticated-orcid":false,"given":"Laurent","family":"Charlet","sequence":"additional","affiliation":[{"name":"Institute of Earth Science (ISTerre), Universit\u00e9 Grenoble Alpes, Universit\u00e9 Savoie Mont Blanc, Centre National de Recherche Scientifique (CNRS), Institut de Recherche pour le D\u00e9veloppement (IRD), Universit\u00e9 Gustave Eiffel, 38000 Grenoble, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacques","family":"Balosso","sequence":"additional","affiliation":[{"name":"Service de Radioth\u00e9rapie, Centre Hospitalo-Universitaire (CHU) de Grenoble, 38000 La Tronche, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4575-5840","authenticated-orcid":false,"given":"Michel","family":"Bourguignon","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM) U1296 Unit \u201cRadiation: Defense, Health, Environment\u201d, 28 Rue Laennec, 69008 Lyon, France"},{"name":"Universit\u00e9 Paris Saclay, Universit\u00e9 Versailles Saint-Quentin (UVSQ), 78180 Montigny le Bretonneux, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7805-1938","authenticated-orcid":false,"given":"Laurent","family":"Pujo-Menjouet","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Claude Bernard Lyon 1, Centre National de Recherche Scientifique (CNRS), Centrale Lyon, Institut National des Sciences Appliqu\u00e9es (INSA) Lyon, Universit\u00e9 Jean Monnet, Institut Camille Jordan(ICJ) UMR5208, Institut National de Recherche en Sciences et Technologies du Num\u00e9rique (INRIA), 69622 Villeurbanne, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1282-1303","authenticated-orcid":false,"given":"Nicolas","family":"Foray","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM) U1296 Unit \u201cRadiation: Defense, Health, Environment\u201d, 28 Rue Laennec, 69008 Lyon, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Berthel, E., Foray, N., and Ferlazzo, M.L. 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