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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,9,1]]},"abstract":"<jats:p>DNA double-strand breaks (DSBs) which arise in G1- or G0-phase normal human cells are repaired by nonhomologous end-joining (NHEJ), a pathway which is important for cell survival but can cause mutations at the break sites. DSB repair by NHEJ is very efficient at high damage levels of 1 or more DSBs per cell, much less efficient at lower damage levels and almost absent if only ~0.05 DSBs per cell are induced. Here, we have analyzed the repair of high and low levels of radiation-induced DSBs in primary fibroblasts from 136 childhood cancer survivors, half of whom developed a second independent tumor later in life, and compared it to the response of primary fibroblasts from 68 individually matched cancer-free individuals. We measured the DSB repair efficiency by quantifying residual \u03b3H2AX foci with an automated scoring system at 24 h after irradiation with doses of 2.5, 5, 10, and 100 mGy, which induce about 0.0625, 0.125, 0.25, and 2.5 DSBs per cell, respectively. Although childhood cancer survivors and cancer-free individuals repaired DSBs after 10 and 100 mGy equally efficiently, their response to lower doses differed drastically. While repair in cancer-free individuals was inefficient after 2.5 mGy, childhood cancer survivors repaired DSBs after this dose as efficiently as after higher doses. These results indicate that most of the childhood cancer survivors analyzed here may harbor a genetic alteration that affects their response to low levels of DSBs. We suggest that such alterations may be either inherited or caused by previous tumor treatments.<\/jats:p>","DOI":"10.1073\/pnas.2603379123","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T16:33:41Z","timestamp":1787762021000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":0,"title":["Repair of DNA double-strand breaks after low radiation doses in childhood cancer survivors and matched cancer-free individuals"],"prefix":"10.1073","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3596-4910","authenticated-orcid":false,"given":"Johanna","family":"Mirsch","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05n911h24","id-type":"ROR","asserted-by":"publisher"}],"name":"Radiation Biology and DNA Repair, Technical University of Darmstadt","place":["Darmstadt, 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