{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T01:06:08Z","timestamp":1790643968162,"version":"4.1.0"},"reference-count":28,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2018,2,7]],"date-time":"2018-02-07T00:00:00Z","timestamp":1517961600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004590","name":"Helse Midt-Norge","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004590","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":[[2018,3]]},"abstract":"<jats:p>To ensure genome stability, mammalian cells employ several <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> repair pathways. Nonhomologous <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> end joining (<jats:styled-content style=\"fixed-case\">NHEJ<\/jats:styled-content>) is the <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> repair process that fixes double\u2010strand breaks throughout the cell cycle. <jats:styled-content style=\"fixed-case\">NHEJ<\/jats:styled-content> is involved in the development of B and T lymphocytes through its function in V(D)J recombination and class switch recombination (<jats:styled-content style=\"fixed-case\">CSR<\/jats:styled-content>). <jats:styled-content style=\"fixed-case\">NHEJ<\/jats:styled-content> consists of several core and accessory factors, including Ku70, Ku80, <jats:styled-content style=\"fixed-case\">XRCC<\/jats:styled-content>4, <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> ligase 4, <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">PK<\/jats:styled-content>cs, Artemis, and <jats:styled-content style=\"fixed-case\">XLF<\/jats:styled-content>. Paralog of <jats:styled-content style=\"fixed-case\">XRCC<\/jats:styled-content>4 and <jats:styled-content style=\"fixed-case\">XLF<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">PAXX<\/jats:styled-content>) is the recently described accessory <jats:styled-content style=\"fixed-case\">NHEJ<\/jats:styled-content> factor that structurally resembles <jats:styled-content style=\"fixed-case\">XRCC<\/jats:styled-content>4 and <jats:styled-content style=\"fixed-case\">XLF<\/jats:styled-content> and interacts with Ku70\/Ku80. To determine the physiological role of <jats:styled-content style=\"fixed-case\">PAXX<\/jats:styled-content> in mammalian cells, we purchased and characterized a set of custom\u2010generated and commercially available <jats:styled-content style=\"fixed-case\">NHEJ<\/jats:styled-content>\u2010deficient human haploid <jats:styled-content style=\"fixed-case\">HAP<\/jats:styled-content>1 cells, <jats:italic><jats:styled-content style=\"fixed-case\">PAXX<\/jats:styled-content><\/jats:italic><jats:sup><jats:italic>\u0394<\/jats:italic><\/jats:sup><jats:italic>, <jats:styled-content style=\"fixed-case\">XRCC<\/jats:styled-content>4<\/jats:italic><jats:sup><jats:italic>\u0394<\/jats:italic><\/jats:sup>, and <jats:italic><jats:styled-content style=\"fixed-case\">XLF<\/jats:styled-content><\/jats:italic><jats:sup><jats:italic>\u0394<\/jats:italic><\/jats:sup>. In our studies, <jats:styled-content style=\"fixed-case\">HAP<\/jats:styled-content>1 <jats:italic><jats:styled-content style=\"fixed-case\">PAXX<\/jats:styled-content><\/jats:italic><jats:sup><jats:italic>\u0394<\/jats:italic><\/jats:sup> cells demonstrated modest sensitivity to <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> damage, which was comparable to wild\u2010type controls. By contrast, <jats:italic><jats:styled-content style=\"fixed-case\">XRCC<\/jats:styled-content>4<\/jats:italic><jats:sup><jats:italic>\u0394<\/jats:italic><\/jats:sup> and <jats:italic><jats:styled-content style=\"fixed-case\">XLF<\/jats:styled-content><\/jats:italic><jats:sup><jats:italic>\u0394<\/jats:italic><\/jats:sup> <jats:styled-content style=\"fixed-case\">HAP<\/jats:styled-content>1 cells possessed significant <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> repair defects measured as sensitivity to double\u2010strand break inducing agents and chromosomal breaks. To investigate the role of <jats:styled-content style=\"fixed-case\">PAXX<\/jats:styled-content> in <jats:styled-content style=\"fixed-case\">CSR<\/jats:styled-content>, we generated and characterized <jats:italic>Paxx<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> and <jats:italic>Aid<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> murine lymphoid <jats:styled-content style=\"fixed-case\">CH<\/jats:styled-content>12F3 cells. <jats:styled-content style=\"fixed-case\">CSR<\/jats:styled-content> to IgA was nearly at wild\u2010type levels in the <jats:italic>Paxx<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> cells and completely ablated in the absence of activation\u2010induced cytidine deaminase (<jats:styled-content style=\"fixed-case\">AID<\/jats:styled-content>). In addition, <jats:italic>Paxx<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> <jats:styled-content style=\"fixed-case\">CH<\/jats:styled-content>12F3 cells were hypersensitive to zeocin when compared to wild\u2010type controls. We concluded that <jats:italic>Paxx<\/jats:italic>\u2010deficient mammalian cells maintain robust <jats:styled-content style=\"fixed-case\">NHEJ<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">CSR<\/jats:styled-content>.<\/jats:p>","DOI":"10.1002\/2211-5463.12380","type":"journal-article","created":{"date-parts":[[2018,1,16]],"date-time":"2018-01-16T17:04:18Z","timestamp":1516122258000},"page":"442-448","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Robust <scp>DNA<\/scp> repair in <scp>PAXX<\/scp>\u2010deficient mammalian cells"],"prefix":"10.1002","volume":"8","author":[{"given":"Alisa","family":"Dewan","sequence":"first","affiliation":[{"name":"Department of Clinical and Molecular Medicine (IKOM) Norwegian University of Science and Technology Trondheim 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