{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T22:01:42Z","timestamp":1791237702721,"version":"4.1.0"},"reference-count":35,"publisher":"Radiation Research Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Radiation Research"],"published-print":{"date-parts":[[2025,11,17]]},"abstract":"<jats:p>DNA double-strand breaks (DSBs) are the most severe type of DNA damage in living organisms and are primarily repaired by two pathways: non-homologous end joining (NHEJ) and homologous recombination (HR). DNA ligase IV (LIG4) is essential for the final step of NHEJ, where it facilitates the rejoining of DSBs. Loss-of-function mutations in the LIG4 gene result in LIG4 syndrome, a condition characterized by combined immunodeficiency, developmental delay, microcephaly and radiosensitivity. In this study, we investigated cellular senescence, radiosensitivity, and X-ray radiation-induced chromosome aberrations induced in newly developed Lig4 mutant (Lig4W447C\/W447C) mouse cells. The results showed that Lig4W447C\/W447C cells exhibited accelerated cellular senescence, possibly due to increased accumulation of spontaneous DSBs. Radiosensitivity assays revealed that Lig4W447C\/W447C cells were four times more radiosensitive than wild-type cells. Moreover, analysis of both X-ray radiation-induced chromatid-type and chromosome-type aberrations revealed that both break-type aberrations (e.g., fragments) and exchange-type aberrations (e.g., dicentrics) were increased in Lig4W447C\/W447C cells compared to wild-type cells. These results suggest that in addition to causing inefficient DNA break, end-joining, the novel mutation in Lig4 may promote misrejoining of X-ray radiation-induced DSBs.<\/jats:p>","DOI":"10.1667\/rade-25-00128","type":"journal-article","created":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T00:01:30Z","timestamp":1763337690000},"page":"70-77","source":"Crossref","is-referenced-by-count":1,"title":["Promoted Misrejoining of X-ray Radiation-induced DNA Double-Strand Breaks in Novel DNA Ligase IV-Deficient Mouse Cells"],"prefix":"10.1667","volume":"205","author":[{"given":"Maiko","family":"Kawata","sequence":"first","affiliation":[{"name":"Laboratory of Radiation Biology, Department of Biological Science, Graduate School of Science, Osaka Metropolitan University, 1-2 Gakuen-cho, Naka-ku, Sakai, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazunori","family":"Shiraishi","sequence":"additional","affiliation":[{"name":"Laboratory of Radiation Biology, Department of Biological Science, Graduate School of Science, Osaka Metropolitan University, 1-2 Gakuen-cho, Naka-ku, Sakai, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Izumi","family":"Satake","sequence":"additional","affiliation":[{"name":"Laboratory of Radiation Biology, Department of Biological Science, Graduate School of Science, Osaka Metropolitan University, 1-2 Gakuen-cho, Naka-ku, Sakai, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukako","family":"Hirato","sequence":"additional","affiliation":[{"name":"Laboratory of Radiation Biology, Department of Biological Science, Graduate School of Science, Osaka Metropolitan University, 1-2 Gakuen-cho, Naka-ku, Sakai, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Yamashita","sequence":"additional","affiliation":[{"name":"Department of Hematology\/Oncology, Wakayama Medical University, 811-1 Kimiidera, Wakayama, Wakayama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideki","family":"Kosako","sequence":"additional","affiliation":[{"name":"Department of Hematology\/Oncology, Wakayama Medical University, 811-1 Kimiidera, Wakayama, Wakayama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Izumi","family":"Sasaki","sequence":"additional","affiliation":[{"name":"Department of Immunology, Institute of Advanced Medicine, Wakayama Medical University, 811-1 Kimiidera, Wakayama, Wakayama 641-8509, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinobu","family":"Tamura","sequence":"additional","affiliation":[{"name":"First Department of Internal Medicine, Wakayama Medical University, 811-1 Kimiidera, Wakayama, Wakayama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuneyasu","family":"Kaisho","sequence":"additional","affiliation":[{"name":"Department of Immunology, Institute of Advanced Medicine, Wakayama Medical University, 811-1 Kimiidera, Wakayama, Wakayama 641-8509, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seiji","family":"Kodama","sequence":"additional","affiliation":[{"name":"Laboratory of Radiation Biology, Department of Biological Science, Graduate School of Science, Osaka Metropolitan University, 1-2 Gakuen-cho, Naka-ku, Sakai, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1243","reference":[{"key":"22","unstructured":"K Rothkamm, M Kuhne, PA Jeggo, et al.  \"Cancer Res.\"  61, \"Radiation-induced genomic rearrangements formed by nonhomologous end-joining of DNA double-strand breaks.\" 3886 (2001)"},{"key":"30","doi-asserted-by":"crossref","unstructured":"D Simsek  and M Jasin  \"Nat Struct Mol Biol.\"  17, \"Alternative end-joining is suppressed by the canonical NHEJ component Xrcc4-ligase IV during chromosomal translocation formation.\" 410 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Chen, et al.  \"Nature.\"  404, \"DNA repair protein Ku80 suppresses chromosomal aberrations and malignant transformation.\" 510 (2000)","DOI":"10.1038\/35006670"}],"container-title":["Radiation Research"],"original-title":[],"link":[{"URL":"https:\/\/radiation-research.kglmeridian.com\/view\/journals\/rare\/aop\/article-10.1667-RADE-25-00128\/article-10.1667-RADE-25-00128.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/meridian.allenpress.com\/radiation-research\/article-pdf\/doi\/10.1667\/RADE-25-00128\/3545970\/10.1667_rade-25-00128.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/radiation-research.kglmeridian.com\/downloadpdf\/journals\/rare\/aop\/article-10.1667-RADE-25-00128\/article-10.1667-RADE-25-00128.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/radiation-research.kglmeridian.com\/downloadpdf\/journals\/rare\/aop\/article-10.1667-RADE-25-00128\/article-10.1667-RADE-25-00128.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T21:48:42Z","timestamp":1791236922000},"score":1,"resource":{"primary":{"URL":"https:\/\/bioone.org\/journals\/radiation-research\/volume-205\/issue-1\/RADE-25-00128\/Promoted-Misrejoining-of-X-ray-Radiation-induced-DNA-Double-Strand\/10.1667\/RADE-25-00128.full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,17]]},"references-count":35,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1,1]]}},"URL":"https:\/\/doi.org\/10.1667\/rade-25-00128","relation":{},"ISSN":["0033-7587","1938-5404"],"issn-type":[{"value":"0033-7587","type":"print"},{"value":"1938-5404","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,17]]}}}