{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T16:42:35Z","timestamp":1785775355641,"version":"3.56.0"},"reference-count":27,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2024,11,16]],"date-time":"2024-11-16T00:00:00Z","timestamp":1731715200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Polish National Agency for Academic Exchange","award":["PPN\/STA\/2021\/1\/00019\/U\/00001"],"award-info":[{"award-number":["PPN\/STA\/2021\/1\/00019\/U\/00001"]}]},{"name":"Polish National Agency for Academic Exchange","award":["2019\/35\/O\/NZ3\/03039"],"award-info":[{"award-number":["2019\/35\/O\/NZ3\/03039"]}]},{"name":"Polish National Science Centre","award":["PPN\/STA\/2021\/1\/00019\/U\/00001"],"award-info":[{"award-number":["PPN\/STA\/2021\/1\/00019\/U\/00001"]}]},{"name":"Polish National Science Centre","award":["2019\/35\/O\/NZ3\/03039"],"award-info":[{"award-number":["2019\/35\/O\/NZ3\/03039"]}]},{"name":"Commissariat General \u00e0 l\u2019Investissement","award":["PPN\/STA\/2021\/1\/00019\/U\/00001"],"award-info":[{"award-number":["PPN\/STA\/2021\/1\/00019\/U\/00001"]}]},{"name":"Commissariat General \u00e0 l\u2019Investissement","award":["2019\/35\/O\/NZ3\/03039"],"award-info":[{"award-number":["2019\/35\/O\/NZ3\/03039"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Marfan syndrome (MFS) is an autosomal dominant connective-tissue disorder affecting multiple systems, such as skeletal, cardiovascular, and ocular systems. MFS is predominantly caused by mutations in the FBN1 gene, which encodes the fibrillin-1 protein, crucial for connective-tissue integrity. FBN1 mutations lead to defective fibrillin, resulting in structurally compromised connective tissues. Additionally, these mutations cause aberrant TGF-\u03b2 expression, contributing to vascular issues and increased susceptibility to radiation-induced fibrosis. Studies about the potential radiosensitivity of MFS are rare and generally limited to case reports. Here, we aimed to investigate the radiation-induced ATM nucleo-shuttling (RIANS) model to explore the molecular and cellular radiation response in fibroblasts from MFS patients. The results showed that the MFS fibroblast cell lines tested are associated with moderate but significant radiosensitivity, high yield of micronuclei, and impaired recognition of DNA double-strand breaks (DSBs) caused by a diminished RIANS. The diminished RIANS is supported by the sequestration of ATM protein in the cytoplasm not only by mutated FBN1 protein but also by overexpressed TGF-\u03b2. This report is the first molecular and cellular characterization of the radiation response of MFS fibroblasts and highlights the importance of the FBN1-TGF-\u03b2 complex after irradiation.<\/jats:p>","DOI":"10.3390\/ijms252212313","type":"journal-article","created":{"date-parts":[[2024,11,18]],"date-time":"2024-11-18T04:07:09Z","timestamp":1731902829000},"page":"12313","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Influence of the Nucleo-Shuttling of the ATM Protein on the Response of Skin Fibroblasts from Marfan Syndrome to Ionizing Radiation"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2253-8587","authenticated-orcid":false,"given":"Dagmara","family":"Jakubowska","sequence":"first","affiliation":[{"name":"Inserm, U1296 Unit, Radiation: Defense, Health and Environment, 28 rue Laennec, 69008 Lyon, France"},{"name":"Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, ul. Wybrze\u017ce Armii Krajowej 15, 44-100 Gliwice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6772-6947","authenticated-orcid":false,"given":"Jo\u00eblle","family":"Al-Choboq","sequence":"additional","affiliation":[{"name":"Inserm, U1296 Unit, Radiation: Defense, Health and Environment, 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, 28 rue Laennec, 69008 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"Bourguignon","sequence":"additional","affiliation":[{"name":"Inserm, U1296 Unit, Radiation: Defense, Health and Environment, 28 rue Laennec, 69008 Lyon, France"},{"name":"D\u00e9partement de Biophysique et M\u00e9decine Nucl\u00e9aire, Universit\u00e9 Paris Saclay, Versailles St. Quentin-en-Yvelines, 78035 Versailles, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1225-2355","authenticated-orcid":false,"given":"Dorota","family":"Slonina","sequence":"additional","affiliation":[{"name":"Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, ul. Wybrze\u017ce Armii Krajowej 15, 44-100 Gliwice, Poland"}],"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, 28 rue Laennec, 69008 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2752","DOI":"10.7150\/ijms.60685","article-title":"The Molecular Genetics of Marfan Syndrome","volume":"18","author":"Du","year":"2021","journal-title":"Int. J. Med. Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1111\/j.1745-7599.2009.00461.x","article-title":"Marfan syndrome","volume":"21","author":"Gonzales","year":"2009","journal-title":"J. Am. Acad. 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