{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:19:06Z","timestamp":1784557146153,"version":"3.55.0"},"reference-count":28,"publisher":"Bioscientifica","issue":"4","license":[{"start":{"date-parts":[[2024,7,24]],"date-time":"2024-07-24T00:00:00Z","timestamp":1721779200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["etj.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,7,24]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      Ionizing radiation generates genomic instability by promoting the accumulation of chromosomal rearrangements. The oncogenic translocation\n                      <jats:italic>RET\/PTC1<\/jats:italic>\n                      is present in more than 70% of radiation-induced thyroid cancers. Both\n                      <jats:italic>RET<\/jats:italic>\n                      and\n                      <jats:italic>CCDC6<\/jats:italic>\n                      , the genes implicated in\n                      <jats:italic>RET\/PTC1<\/jats:italic>\n                      , are found within common fragile sites \u2013 chromosomal regions prone to DNA breakage during slight replication stress. Given that irradiated cells become more susceptible to genomic destabilization due to the accumulation of replication-stress-related double-strand breaks (DSBs), we explored whether\n                      <jats:italic>RET<\/jats:italic>\n                      and\n                      <jats:italic>CCDC6<\/jats:italic>\n                      exhibit DNA breakage under replicative stress several days post-irradiation of thyroid cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We analyzed the dynamic of DNA replication in human thyroid epithelial cells (HThy-ori-3.1) 4 days post a 5-Gy exposure using molecular DNA combing. The DNA replication schedule was evaluated through replication-timing experiments. We implemented a ChIP-qPCR assay to determine whether the\n                      <jats:italic>RET<\/jats:italic>\n                      and\n                      <jats:italic>CCDC6<\/jats:italic>\n                      genes break following irradiation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Our study indicates that replicative stress, occurring several days post-irradiation in thyroid cells, primarily causes DSBs in the\n                      <jats:italic>RET<\/jats:italic>\n                      gene. We discovered that both the\n                      <jats:italic>RET<\/jats:italic>\n                      and\n                      <jats:italic>CCDC6<\/jats:italic>\n                      genes undergo late replication in thyroid cells. However, only\n                      <jats:italic>RET<\/jats:italic>\n                      \u2019s replication rate is notably delayed after irradiation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      The findings suggest that post-irradiation in the\n                      <jats:italic>RET<\/jats:italic>\n                      gene causes a breakage in the replication fork, which could potentially invade another genomic area, including\n                      <jats:italic>CCDC6<\/jats:italic>\n                      . As a result, this could greatly contribute to the high prevalence of chromosomal\n                      <jats:italic>RET\/PTC<\/jats:italic>\n                      rearrangements seen in patients exposed to external radiation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1530\/etj-24-0028","type":"journal-article","created":{"date-parts":[[2024,7,24]],"date-time":"2024-07-24T14:13:45Z","timestamp":1721830425000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-16","source":"Crossref","is-referenced-by-count":0,"title":["A post-irradiation-induced replication stress promotes RET proto-oncogene breakage"],"prefix":"10.1530","volume":"13","author":[{"given":"Fabio","family":"Hecht","sequence":"first","affiliation":[{"name":"Universit\u00e9 Paris-Saclay, Orsay, France"},{"name":"UMR 9019 CNRS F-94805 Villejuif, France"},{"name":"Gustave Roussy, Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Valerio","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris-Saclay, Orsay, France"},{"name":"UMR 9019 CNRS F-94805 Villejuif, France"},{"name":"Gustave Roussy, Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos Frederico Lima","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris-Saclay, Orsay, France"},{"name":"UMR 9019 CNRS F-94805 Villejuif, France"},{"name":"Gustave Roussy, Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marylin","family":"Harinquet","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris-Saclay, Orsay, France"},{"name":"UMR 9019 CNRS F-94805 Villejuif, France"},{"name":"Gustave Roussy, Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rabii","family":"Ameziane El Hassani","sequence":"additional","affiliation":[{"name":"Laboratoire de Biologie des Pathologies Humaines \u2018BioPatH\u2019, Universit\u00e9 Mohammed V de Rabat, Facult\u00e9 des Sciences, BP1014 Rabat, 10001, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise P","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Fisiologia End\u00f3crina Doris Rosenthal, nstituto de Biof\u00edsica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephane","family":"Koundrioukoff","sequence":"additional","affiliation":[{"name":"UMR 9019 CNRS F-94805 Villejuif, France"},{"name":"Gustave Roussy, Villejuif, France"},{"name":"Sorbonne Universit\u00e9, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Charles","family":"Cadoret","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, CNRS, Institut Jacques Monod, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3898-8267","authenticated-orcid":true,"given":"Corinne","family":"Dupuy","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris-Saclay, Orsay, France"},{"name":"UMR 9019 CNRS F-94805 Villejuif, France"},{"name":"Gustave Roussy, Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"bib1","series-title":"Endocrine Reviews","first-page":"756","article-title":"Exposing the thyroid to radiation: a review of its current extent, risks, and implications","volume":"31","author":"Sinnott","year":"2010","unstructured":"Sinnott BRon E & Schneider AB. 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