{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T14:50:48Z","timestamp":1790779848366,"version":"4.1.0"},"reference-count":51,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,1,29]],"date-time":"2022-01-29T00:00:00Z","timestamp":1643414400000},"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"],"award-info":[{"award-number":["INDIRA"]}],"id":[{"id":"10.13039\/501100006072","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002830","name":"Centre National d'\u00c9tudes Spatiales","doi-asserted-by":"publisher","award":["ATHENA and BERNADOTTE"],"award-info":[{"award-number":["ATHENA and BERNADOTTE"]}],"id":[{"id":"10.13039\/501100002830","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Association pour la Recherche sur l'Ataxie Telangiectasie","award":["COPERNIC"],"award-info":[{"award-number":["COPERNIC"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Usher syndrome (USH) is a rare autosomal recessive disease characterized by the combination of hearing loss, visual impairment due to retinitis pigmentosa, and in some cases vestibular dysfunctions. Studies published in the 1980s reported that USH is associated with cellular radiosensitivity. However, the molecular basis of this particular phenotype has not yet been documented. The aim of this study was therefore to document the radiosensitivity of USH1\u2014a subset of USH\u2014by examining the radiation-induced nucleo-shuttling of ATM (RIANS), as well as the functionality of the repair and signaling pathways of the DNA double-strand breaks (DSBs) in three skin fibroblasts derived from USH1 patients. The clonogenic cell survival, the micronuclei, the nuclear foci formed by the phosphorylated forms of the X variant of the H2A histone (\u0263H2AX), the phosphorylated forms of the ATM protein (pATM), and the meiotic recombination 11 nuclease (MRE11) were used as cellular and molecular endpoints. The interaction between the ATM and USH1 proteins was also examined by proximity ligation assay. The results showed that USH1 fibroblasts were associated with moderate but significant radiosensitivity, high yield of micronuclei, and impaired DSB recognition but normal DSB repair, likely caused by a delayed RIANS, suggesting a possible sequestration of ATM by some USH1 proteins overexpressed in the cytoplasm. To our knowledge, this report is the first radiobiological characterization of cells from USH1 patients at both molecular and cellular scales.<\/jats:p>","DOI":"10.3390\/ijms23031570","type":"journal-article","created":{"date-parts":[[2022,1,29]],"date-time":"2022-01-29T23:02:06Z","timestamp":1643497326000},"page":"1570","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Usher Syndrome Belongs to the Genetic Diseases Associated with Radiosensitivity: Influence of the ATM Protein Kinase"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6772-6947","authenticated-orcid":false,"given":"Jo\u00eblle","family":"Al-Choboq","sequence":"first","affiliation":[{"name":"Inserm, U1296 Unit, Radiation: Defense, Health and Environment, Centre L\u00e9on-B\u00e9rard, 28 rue Laennec, 69008 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e9lanie L.","family":"Ferlazzo","sequence":"additional","affiliation":[{"name":"Inserm, U1296 Unit, Radiation: Defense, Health and Environment, Centre L\u00e9on-B\u00e9rard, 28 rue Laennec, 69008 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laur\u00e8ne","family":"Sonzogni","sequence":"additional","affiliation":[{"name":"Inserm, U1296 Unit, Radiation: Defense, Health and Environment, Centre L\u00e9on-B\u00e9rard, 28 rue Laennec, 69008 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adeline","family":"Granzotto","sequence":"additional","affiliation":[{"name":"Inserm, U1296 Unit, Radiation: Defense, Health and Environment, Centre L\u00e9on-B\u00e9rard, 28 rue Laennec, 69008 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2860-9235","authenticated-orcid":false,"given":"Laura","family":"El-Nachef","sequence":"additional","affiliation":[{"name":"Inserm, U1296 Unit, Radiation: Defense, Health and Environment, Centre L\u00e9on-B\u00e9rard, 28 rue Laennec, 69008 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mira","family":"Maalouf","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Faculty of Sciences II, Lebanese University, Fanar 1202, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7057-1840","authenticated-orcid":false,"given":"Elise","family":"Berthel","sequence":"additional","affiliation":[{"name":"Inserm, U1296 Unit, Radiation: Defense, Health and Environment, Centre L\u00e9on-B\u00e9rard, 28 rue Laennec, 69008 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1282-1303","authenticated-orcid":false,"given":"Nicolas","family":"Foray","sequence":"additional","affiliation":[{"name":"Inserm, U1296 Unit, Radiation: Defense, Health and Environment, Centre L\u00e9on-B\u00e9rard, 28 rue Laennec, 69008 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"565216","DOI":"10.3389\/fgene.2020.565216","article-title":"Usher Syndrome: Genetics and Molecular Links of Hearing Loss and Directions for Therapy","volume":"11","author":"Whatley","year":"2020","journal-title":"Front. 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