{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T10:42:46Z","timestamp":1787568166236,"version":"build-2736575974"},"reference-count":51,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2024,7,26]],"date-time":"2024-07-26T00:00:00Z","timestamp":1721952000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,7,26]],"date-time":"2024-07-26T00:00:00Z","timestamp":1721952000000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,7,26]],"date-time":"2024-07-26T00:00:00Z","timestamp":1721952000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31170821"],"award-info":[{"award-number":["31170821"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007128","name":"Natural Science Foundation of Shaanxi Province","doi-asserted-by":"publisher","award":["2022JZ-44"],"award-info":[{"award-number":["2022JZ-44"]}],"id":[{"id":"10.13039\/501100007128","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31370874"],"award-info":[{"award-number":["31370874"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81670157"],"award-info":[{"award-number":["81670157"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Xi 'an Jiaotong University Medical \"Basic - Clinical\" Fusion Innovation Project","award":["YXJLRH2022012"],"award-info":[{"award-number":["YXJLRH2022012"]}]},{"name":"Xi 'an Jiaotong University Medical \"Basic - Clinical\" Fusion Innovation Project","award":["YJSCX-2024-007"],"award-info":[{"award-number":["YJSCX-2024-007"]}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>\n                    The evolutionary conservation of non-core RAG regions suggests significant roles that might involve quantitative or qualitative alterations in RAG activity. Off-target V(D)J recombination contributes to lymphomagenesis and is exacerbated by RAG2\u2019 C-terminus absence in\n                    <jats:italic>\n                      Tp53\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    mice thymic lymphomas. However, the genomic stability effects of non-core regions from both\n                    <jats:italic>\n                      Rag1\n                      <jats:sup>c\/c<\/jats:sup>\n                    <\/jats:italic>\n                    and\n                    <jats:italic>\n                      Rag2\n                      <jats:sup>c\/c<\/jats:sup>\n                    <\/jats:italic>\n                    in\n                    <jats:italic>BCR-ABL1<\/jats:italic>\n                    <jats:sup>+<\/jats:sup>\n                    B-lymphoblastic leukemia (\n                    <jats:italic>BCR-ABL1<\/jats:italic>\n                    <jats:sup>+<\/jats:sup>\n                    B-ALL), the characteristics, and mechanisms of non-core regions in suppressing off-target V(D)J recombination remain unclear. Here, we established three mouse models of\n                    <jats:italic>BCR-ABL1<\/jats:italic>\n                    <jats:sup>+<\/jats:sup>\n                    B-ALL in mice expressing full-length RAG (Rag\n                    <jats:sup>f\/f<\/jats:sup>\n                    ), core RAG1 (Rag1\n                    <jats:sup>c\/c<\/jats:sup>\n                    ), and core RAG2 (Rag2\n                    <jats:sup>c\/c<\/jats:sup>\n                    ). The\n                    <jats:italic>\n                      Rag\n                      <jats:sup>c\/c<\/jats:sup>\n                    <\/jats:italic>\n                    (\n                    <jats:italic>\n                      Rag1\n                      <jats:sup>c\/c<\/jats:sup>\n                    <\/jats:italic>\n                    and\n                    <jats:italic>\n                      Rag2\n                      <jats:sup>c\/c<\/jats:sup>\n                    <\/jats:italic>\n                    ) leukemia cells exhibited greater malignant tumor characteristics compared to\n                    <jats:italic>\n                      Rag\n                      <jats:sup>f\/f<\/jats:sup>\n                    <\/jats:italic>\n                    cells. Additionally,\n                    <jats:italic>\n                      Rag\n                      <jats:sup>c\/c<\/jats:sup>\n                    <\/jats:italic>\n                    cells showed higher frequency of off-target V(D)J recombination and oncogenic mutations than\n                    <jats:italic>\n                      Rag\n                      <jats:sup>f\/f<\/jats:sup>\n                    <\/jats:italic>\n                    . We also revealed decreased RAG cleavage accuracy in\n                    <jats:italic>\n                      Rag\n                      <jats:sup>c\/c<\/jats:sup>\n                    <\/jats:italic>\n                    cells and a smaller recombinant size in\n                    <jats:italic>\n                      Rag1\n                      <jats:sup>c\/c<\/jats:sup>\n                    <\/jats:italic>\n                    cells, which could potentially exacerbate off-target V(D)J recombination in\n                    <jats:italic>\n                      Rag\n                      <jats:sup>c\/c<\/jats:sup>\n                    <\/jats:italic>\n                    cells. In conclusion, these findings indicate that the non-core RAG regions, particularly the non-core region of RAG1, play a significant role in preserving V(D)J recombination precision and genomic stability in\n                    <jats:italic>BCR-ABL1<\/jats:italic>\n                    <jats:sup>+<\/jats:sup>\n                    B-ALL.\n                  <\/jats:p>","DOI":"10.7554\/elife.91030","type":"journal-article","created":{"date-parts":[[2023,11,1]],"date-time":"2023-11-01T13:51:16Z","timestamp":1698846676000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.91030","source":"Crossref","is-referenced-by-count":3,"title":["RAG1 and RAG2 non-core regions are implicated in leukemogenesis and off-target V(D)J recombination in BCR-ABL1-driven B-cell lineage lymphoblastic leukemia"],"prefix":"10.7554","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-7565-8941","authenticated-orcid":true,"given":"Xiaozhuo","family":"Yu","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/017zhmm22","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pathogenic Biology and Immunology, School of Basic Medical Sciences, Xi\u2019an Jiaotong University Health Science Center","place":["Xi'an, China"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"given":"Wen","family":"Zhou","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/017zhmm22","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pathogenic Biology and Immunology, School of Basic Medical Sciences, 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