{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T18:40:25Z","timestamp":1760467225646,"version":"build-2065373602"},"reference-count":88,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"908","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Signal."],"published-print":{"date-parts":[[2025,10,14]]},"abstract":"<jats:p>\n            Antigen receptor diversity depends on the assembly of variable (V), diverse (D), and joining (J) exons in genes encoding immunoglobulins (Igs) and T cell receptors (TCRs). During V(D)J recombination, DNA double-strand breaks (DSBs) introduced by the RAG1\/2 nuclease complex are repaired by the process of nonhomologous end-joining (NHEJ). We hypothesized that functional redundancies between NHEJ and the chromatin DSB response, which depends on the kinase ATM, potentially masked the activity of additional factors that regulate V(D)J recombination. We performed targeted CRISPR-Cas9 knockout screens for genes implicated in V(D)J recombination in pro-B cells that were either untreated or treated with an ATM inhibitor. We found that loss of the RNA\/DNA helicase senataxin (SETX) impaired V(D)J recombination and led to the formation of aberrant hybrid joints between coding ends and signal ends, both in vitro and in mice. The loss of SETX in a background deficient in the NHEJ factor XLF or in which ATM was inhibited led to substantial impairment of V(D)J recombination and to the presence of unsealed coding ends. SETX limited aberrant activation-induced cytidine deaminase (AID)\u2013induced DNA end-joining between\n            <jats:italic toggle=\"yes\">Igh<\/jats:italic>\n            -containing alleles during the process of class-switch recombination. Together, our findings reveal a previously uncharacterized role for SETX in promoting recombination fidelity during antigen receptor gene diversification.\n          <\/jats:p>","DOI":"10.1126\/scisignal.adv8801","type":"journal-article","created":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T17:58:10Z","timestamp":1760464690000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Senataxin promotes recombination fidelity during antigen receptor gene diversification"],"prefix":"10.1126","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-5842-3157","authenticated-orcid":true,"given":"Alice Billie","family":"Libri","sequence":"first","affiliation":[{"name":"Institut Pasteur, Universit\u00e9 Paris Cit\u00e9, INSERM U1223, \u00c9quipe Labellis\u00e9e Ligue Contre Le Cancer, Genome Integrity, Immunity and Cancer Unit, 75015 Paris, France."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0125-8201","authenticated-orcid":true,"given":"Jinglong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, School of Medicine, Stanford University, CA 94305, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4908-8616","authenticated-orcid":true,"given":"Timea","family":"Marton","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Universit\u00e9 Paris Cit\u00e9, INSERM U1223, \u00c9quipe Labellis\u00e9e Ligue Contre Le Cancer, Genome Integrity, Immunity and Cancer Unit, 75015 Paris, France."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1777-5254","authenticated-orcid":true,"given":"Wei","family":"Yu","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Universit\u00e9 Paris Cit\u00e9, INSERM U1223, \u00c9quipe Labellis\u00e9e Ligue Contre Le Cancer, Genome Integrity, Immunity and Cancer Unit, 75015 Paris, France."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4085-1446","authenticated-orcid":true,"given":"Fran\u00e7ois","family":"Dossin","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Universit\u00e9 Paris Cit\u00e9, INSERM U1223, \u00c9quipe Labellis\u00e9e Ligue Contre Le Cancer, Genome Integrity, Immunity and Cancer Unit, 75015 Paris, France."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2872-4468","authenticated-orcid":true,"given":"Gabriel","family":"Balmus","sequence":"additional","affiliation":[{"name":"UK Dementia Research Institute at the University of Cambridge, Cambridge CB2 0AH, UK."},{"name":"Department of Clinical Neurosciences, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0AH, UK."},{"name":"Department of Molecular Neuroscience, Transylvanian Institute of Neuroscience, 400191 Cluj-Napoca, Romania."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernardo","family":"Reina-San-Martin","sequence":"additional","affiliation":[{"name":"Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire (IGBMC), F-67400 Illkirch, France."},{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM), UMR-S 1258, F-67400 Illkirch, France."},{"name":"Centre National de la Recherche Scientifique (CNRS), UMR 7104, F-67400 Illkirch, France."},{"name":"Universit\u00e9 de Strasbourg, IGBMC UMR 7104, UMR-S 1258, F-67400 Illkirch, France."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6963-4931","authenticated-orcid":true,"given":"Richard","family":"Frock","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, School of Medicine, Stanford University, CA 94305, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0622-1149","authenticated-orcid":true,"given":"Chlo\u00e9","family":"Lescale","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Universit\u00e9 Paris Cit\u00e9, INSERM U1223, \u00c9quipe Labellis\u00e9e Ligue Contre Le Cancer, Genome Integrity, Immunity and Cancer Unit, 75015 Paris, France."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9673-9525","authenticated-orcid":true,"given":"Ludovic","family":"Deriano","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Universit\u00e9 Paris Cit\u00e9, INSERM U1223, \u00c9quipe Labellis\u00e9e Ligue Contre Le Cancer, Genome Integrity, Immunity and Cancer Unit, 75015 Paris, France."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"crossref","unstructured":"C. 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