{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T03:18:35Z","timestamp":1772162315133,"version":"3.50.1"},"reference-count":77,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"25","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2025,6,20]]},"abstract":"<jats:p>Nonhomologous end joining (NHEJ) is required for repairing DNA double strand breaks (DSBs) generated by the RAG endonuclease during lymphocyte antigen receptor gene assembly by V(D)J recombination. The ataxia telangiectasia\u2013mutated (ATM) and DNA-dependent protein kinase catalytic subunit (DNA-PKcs) kinases regulate functionally redundant pathways required for NHEJ. Here, we report that loss of the senataxin helicase leads to a strong defect in RAG DSB repair upon inactivation of DNA-PKcs. The NHEJ function of senataxin is redundant with the RECQL5 helicase and the HLTF translocase and is epistatic with ATM. Co-inactivation of ATM, RECQL5, and HLTF results in an NHEJ defect similar to that from the combined deficiency of DNA-PKcs and senataxin or losing senataxin, RECQL5, and HLTF. These data suggest that ATM and DNA-PKcs regulate the functions of senataxin and RECQL5\/HLTF, respectively, to provide redundant support for NHEJ.<\/jats:p>","DOI":"10.1126\/sciadv.ads5272","type":"journal-article","created":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T13:58:33Z","timestamp":1750427913000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":1,"title":["Senataxin and DNA-PKcs redundantly promote non-homologous end joining repair of DNA double strand breaks during V(D)J recombination"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6404-2099","authenticated-orcid":true,"given":"Bo-Ruei","family":"Chen","sequence":"first","affiliation":[{"name":"Division of Hematology and Oncology, University of Alabama at Birmingham, Birmingham, AL 35233, USA."},{"name":"O\u2019Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL 35233, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2086-3902","authenticated-orcid":true,"given":"Thu","family":"Pham","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, University of Alabama at Birmingham, Birmingham, AL 35233, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7849-1231","authenticated-orcid":true,"given":"Lance D.","family":"Reynolds","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, University of Alabama at Birmingham, Birmingham, AL 35233, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9483-2099","authenticated-orcid":true,"given":"Nghi","family":"Dang","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, University of Alabama at Birmingham, Birmingham, AL 35233, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3859-3839","authenticated-orcid":true,"given":"Yanfeng","family":"Zhang","sequence":"additional","affiliation":[{"name":"O\u2019Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL 35233, USA."},{"name":"Genetics Research Division, University of Alabama at Birmingham, Birmingham, AL 35233, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kimberly","family":"Manalang","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, University of Alabama at Birmingham, Birmingham, AL 35233, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4085-7810","authenticated-orcid":true,"given":"Gabriel","family":"Matos-Rodrigues","sequence":"additional","affiliation":[{"name":"Laboratory of Genome Integrity, National Cancer Institute, Bethesda, MD 20892, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7827-8518","authenticated-orcid":true,"given":"Jason Romero","family":"Neidigk","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, University of Alabama at Birmingham, Birmingham, AL 35233, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8952-7268","authenticated-orcid":true,"given":"Andre","family":"Nussenzweig","sequence":"additional","affiliation":[{"name":"Laboratory of Genome Integrity, National Cancer Institute, Bethesda, MD 20892, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9765-1659","authenticated-orcid":true,"given":"Jessica K.","family":"Tyler","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY 10065, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8295-4462","authenticated-orcid":true,"given":"Barry P.","family":"Sleckman","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, University of Alabama at Birmingham, Birmingham, AL 35233, USA."},{"name":"O\u2019Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL 35233, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(02)00675-X"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2022.886718"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2004.03.015"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.0105-2896.2004.00165.x"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm.2017.48"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1248024"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1004563"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(02)00671-2"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-biochem-080320-110356"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2024.103716"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2016.02.010"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41594-018-0065-1"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2019.11.018"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2020.12.015"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2023.103553"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03458-7"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2021.03.001"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2017.05.015"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2009.04.025"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1013295108"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1019293108"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00308-13"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni870"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature04866"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.68466"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2023.09.024"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkad092"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M115.674002"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2018.06.018"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2015.02.024"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200608077"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.4161\/cc.9.13.12148"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.15252\/embj.201696174"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3132"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2010.12.007"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00441-14"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-50080-y"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.ado3867"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2021.103139"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2021.103211"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature13393"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature09585"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2014.10.024"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-genet-071719-020312"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20081326"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-2776(08)60450-2"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/28.14.2752"},{"issue":"44","key":"e_1_3_2_49_2","article-title":"Transient ATM kinase inhibition disrupts DNA damage-induced sister chromatid exchange","volume":"3","author":"White J. S.","year":"2010","unstructured":"J. S. White, S. Choi, C. J. Bakkenist, Transient ATM kinase inhibition disrupts DNA damage-induced sister chromatid exchange. Sci. Signal. 3, ra44 (2010).","journal-title":"Sci. Signal."},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.01195-12"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-02894-w"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.107603"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.78917"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1609107"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkp147"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2012.05.001"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1080\/10409238.2017.1380597"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600301"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2024.07.018"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2016.05.016"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2017.05.006"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1101951108"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2022.04.014"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2023.103552"},{"key":"e_1_3_2_65_2","doi-asserted-by":"crossref","unstructured":"S. Marshall M. Navarro C. F. R. Ascen\u04abao M. B. Smolka In-depth mapping of DNA-pkcs signaling uncovers conserved features of its kinase specificity. bioRxiv 576037 [Preprint] (2024); www.biorxiv.org\/content\/10.1101\/2024.01.17.576037v1.","DOI":"10.1101\/2024.01.17.576037"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky641"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.68648"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-genet-110410-132435"},{"key":"e_1_3_2_69_2","doi-asserted-by":"publisher","DOI":"10.15252\/embr.201847560"},{"key":"e_1_3_2_70_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2022.932633"},{"key":"e_1_3_2_71_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-21806-y"},{"key":"e_1_3_2_72_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.03.050"},{"key":"e_1_3_2_73_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adn4682"},{"key":"e_1_3_2_74_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0163962"},{"key":"e_1_3_2_75_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.09.079"},{"key":"e_1_3_2_76_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1247005"},{"key":"e_1_3_2_77_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-017-4159-7"},{"key":"e_1_3_2_78_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp394"}],"container-title":["Science Advances"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/sciadv.ads5272","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T13:58:35Z","timestamp":1750427915000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/sciadv.ads5272"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,20]]},"references-count":77,"journal-issue":{"issue":"25","published-print":{"date-parts":[[2025,6,20]]}},"alternative-id":["10.1126\/sciadv.ads5272"],"URL":"https:\/\/doi.org\/10.1126\/sciadv.ads5272","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2024.09.25.615014","asserted-by":"object"}]},"ISSN":["2375-2548"],"issn-type":[{"value":"2375-2548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,20]]},"assertion":[{"value":"2024-08-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-15","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eads5272"}}