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The RAG1 N-terminal region (NTR; aa 1\u2013383) has been implicated in regulatory functions whose influence on V(D)J recombination and lymphocyte development in vivo is poorly understood. We generated mice in which RAG1 lacks ubiquitin ligase activity (P326G), the major site of autoubiquitination (K233R), or its first 215 residues (\u0394215). While few abnormalities were detected in R1.K233R mice, R1.P326G mice exhibit multiple features indicative of reduced recombination efficiency, including an increased Ig\u03ba+:Ig\u03bb+ B cell ratio and decreased recombination of Igh, Ig\u03ba, Ig\u03bb, and Tcrb loci. Previous studies indicate that synapsis of recombining partners during Igh recombination occurs through two pathways: long-range scanning and short-range collision. We find that R1\u0394215 mice exhibit reduced short-range Igh and Tcrb D-to-J recombination. Our findings indicate that the RAG1 NTR regulates V(D)J recombination and lymphocyte development by multiple pathways, including control of the balance between short- and long-range recombination.<\/jats:p>","DOI":"10.1084\/jem.20210250","type":"journal-article","created":{"date-parts":[[2021,8,17]],"date-time":"2021-08-17T13:32:57Z","timestamp":1629207177000},"update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":26,"title":["The RAG1 N-terminal region regulates the efficiency and pathways of synapsis for V(D)J recombination"],"prefix":"10.1084","volume":"218","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2888-5256","authenticated-orcid":true,"given":"Helen A.","family":"Beilinson","sequence":"first","affiliation":[{"name":"Department of Immunobiology, Yale School of Medicine, Yale University, New Haven, CT 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