{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T09:57:48Z","timestamp":1756461468018,"version":"3.37.3"},"reference-count":54,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2023,3,20]],"date-time":"2023-03-20T00:00:00Z","timestamp":1679270400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["Numbers JP15H02817","JP17K20042","JP20H04334"],"award-info":[{"award-number":["Numbers JP15H02817","JP17K20042","JP20H04334"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,5,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Aprataxin (APTX), the product of the causative gene for hereditary neurogenerative syndromes Ataxia-oculomotor apraxia 1 and early onset ataxia with oculomotor apraxia and hypoalbuminemia, has an enzymatic activity of removing adenosine monophosphate from DNA 5\u2032-end, which arises from abortive ligation by DNA ligases. It is also reported that APTX physically binds to XRCC1 and XRCC4, suggesting its involvement in DNA single-strand break repair (SSBR) and DNA double-strand break repair (DSBR) via non-homologous end joining pathway. Although the involvement of APTX in SSBR in association with XRCC1 has been established, the significance of APTX in DSBR and its interaction with XRCC4 have remained unclear. Here, we generated APTX knock-out (APTX\u2212\/\u2212) cell from human osteosarcoma U2OS through CRISPR\/Cas9-mediated genome editing system. APTX\u2212\/\u2212 cells exhibited increased sensitivity toward ionizing radiation (IR) and Camptothecin in association with retarded DSBR, as shown by increased number of retained \u03b3H2AX foci. However, the number of retained 53BP1 foci in APTX\u2212\/\u2212 cell was not discernibly different from wild-type cells, in stark contrast to XRCC4-depleted cells. The recruitment of GFP-tagged APTX (GFP-APTX) to the DNA damage sites was examined by laser micro-irradiation and live-cell imaging analysis using confocal microscope. The accumulation of GFP-APTX on the laser track was attenuated by siRNA-mediated depletion of XRCC1, but not XRCC4. Moreover, the deprivation of APTX and XRCC4 displayed additive inhibitory effects on DSBR after IR exposure and end joining of GFP reporter. These findings collectively suggest that APTX acts in DSBR in a manner distinct from XRCC4.<\/jats:p>","DOI":"10.1093\/jrr\/rrad007","type":"journal-article","created":{"date-parts":[[2023,3,21]],"date-time":"2023-03-21T00:54:31Z","timestamp":1679360071000},"page":"485-495","source":"Crossref","is-referenced-by-count":2,"title":["APTX acts in DNA double-strand break repair in a manner distinct from XRCC4"],"prefix":"10.1093","volume":"64","author":[{"given":"Rikiya","family":"Imamura","sequence":"first","affiliation":[{"name":"Institute of Innovative Research, Tokyo Institute of Technology Laboratory for Zero-Carbon Energy, , 2-12-1 Ookayama, Meguro-ku, Tokyo 152-8550 , Japan"},{"name":"National Cancer Center Research Institute , 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 , Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mizuki","family":"Saito","sequence":"additional","affiliation":[{"name":"Institute of Innovative Research, Tokyo Institute of Technology Laboratory for Zero-Carbon Energy, , 2-12-1 Ookayama, Meguro-ku, Tokyo 152-8550 , Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mikio","family":"Shimada","sequence":"additional","affiliation":[{"name":"Institute of Innovative Research, Tokyo Institute of Technology Laboratory for Zero-Carbon Energy, , 2-12-1 Ookayama, Meguro-ku, Tokyo 152-8550 , Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junya","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"School of Health Science at Narita, International University of Health and Welfare Department of Radiological Sciences, , 4-3 Kozunomori, Narita, Chiba 286-8686 , Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masamichi","family":"Ishiai","sequence":"additional","affiliation":[{"name":"National Cancer Center Research Institute , 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 , Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshihisa","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Institute of Innovative Research, Tokyo Institute of Technology Laboratory for Zero-Carbon Energy, , 2-12-1 Ookayama, Meguro-ku, Tokyo 152-8550 , Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2023,3,20]]},"reference":[{"key":"2023052613403192200_ref1","doi-asserted-by":"crossref","first-page":"102921","DOI":"10.1016\/j.dnarep.2020.102921","article-title":"Mammalian DNA base excision repair: dancing in the moonlight","volume":"93","author":"Caldecott","year":"2020","journal-title":"DNA Repair (Amst)"},{"key":"2023052613403192200_ref2","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1038\/s41580-019-0152-0","article-title":"DNA double-strand break repair-pathway choice in somatic mammalian cells","volume":"20","author":"Scully","year":"2019","journal-title":"Nat Re 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deficiency in DNA non-homologous end-joining","volume":"16","author":"Woodbine","year":"2014","journal-title":"DNA Repair (Amst)"},{"key":"2023052613403192200_ref7","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1038\/nature05164","article-title":"The neurodegenerative disease protein aprataxin resolves abortive DNA ligation intermediates","volume":"443","author":"Ahel","year":"2006","journal-title":"Nature"},{"key":"2023052613403192200_ref8","doi-asserted-by":"crossref","first-page":"9469","DOI":"10.1074\/jbc.M611489200","article-title":"Actions of aprataxin in multiple DNA repair pathways","volume":"282","author":"Rass","year":"2007","journal-title":"J Biol Chem"},{"key":"2023052613403192200_ref9","doi-asserted-by":"crossref","first-page":"13939","DOI":"10.1074\/jbc.M507946200","article-title":"Aprataxin forms a discrete branch in the HIT (histidine triad) superfamily of proteins with both DNA\/RNA binding and nucleotide hydrolase 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