{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T06:34:48Z","timestamp":1757313288560,"version":"3.40.5"},"reference-count":54,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,2,18]],"date-time":"2022-02-18T00:00:00Z","timestamp":1645142400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP16K00554","JP19K12337"],"award-info":[{"award-number":["JP16K00554","JP19K12337"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["FEBS Open Bio"],"published-print":{"date-parts":[[2022,4]]},"abstract":"<jats:p>Radiation and chemotherapy resistance remain some of the greatest challenges in human and veterinary cancer therapies. XRCC4, an essential molecule for nonhomologous end joining repair, is a promising target for radiosensitizers. Genetic variants and mutations of <jats:italic>XRCC4<\/jats:italic> contribute to cancer susceptibility, and <jats:italic>XRCC4<\/jats:italic> is also the causative gene of microcephalic primordial dwarfism (MPD) in humans. The development of clinically effective molecular\u2010targeted drugs requires accurate understanding of the functions and regulatory mechanisms of XRCC4. In this study, we cloned and sequenced the cDNA of feline <jats:italic>XRCC4<\/jats:italic>. Comparative analysis indicated that sequences and post\u2010translational modification sites that are predicted to be involved in regulating the localization of human XRCC4, including the nuclear localization signal, are mostly conserved in feline XRCC4. All examined target amino acids responsible for human MPD are completely conserved in feline XRCC4. Furthermore, we found that the localization of feline XRCC4 dynamically changes during the cell cycle. Soon after irradiation, feline XRCC4 accumulated at laser\u2010induced DNA double\u2010strand break (DSB) sites in both the interphase and mitotic phase, and this accumulation was dependent on the presence of Ku. Additionally, XRCC4 superfamily proteins XLF and PAXX accumulated at the DSB sites. Collectively, these findings suggest that mechanisms regulating the spatiotemporal localization of XRCC4 are crucial for XRCC4 function in humans and cats. Our findings contribute to elucidating the functions of XRCC4 and the role of abnormal XRCC4 in diseases, including cancers and MPD, and may help in developing XRCC4\u2010targeted drugs, such as radiosensitizers, for humans and cats.<\/jats:p>","DOI":"10.1002\/2211-5463.13363","type":"journal-article","created":{"date-parts":[[2022,1,9]],"date-time":"2022-01-09T17:48:37Z","timestamp":1641750517000},"page":"798-810","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Feline XRCC4 undergoes rapid Ku\u2010dependent recruitment to DNA damage sites"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7046-0975","authenticated-orcid":false,"given":"Manabu","family":"Koike","sequence":"first","affiliation":[{"name":"Institute for Quantum Medical Science National Institutes for Quantum Science and Technology Chiba Japan"},{"name":"Department of Regulatory Biology Faculty of Science Saitama 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