The RAG1 N-terminal region regulates the efficiency and pathways of synapsis for V(D)J recombination

Studies of novel RAG1 N-terminal region mutants reveal a role for the first 215 amino acids in establishing the balance between short- and long-range V(D)J recombination and a distinct role for RAG1 ubiquitin ligase activity in promoting efficient recombination and lymphocyte development. Overall design: We generated mice in which RAG1 lacks ubiquitin ligase activity (P326G), the major site of autoubiquitination (K233R), or its first 215 residues (d215). We analyzed the Igh repertoire of these mice in bone marrow (B220+ IgM-) and splenic (B220+) B cells using HTGTS-Rep-seq with Jh1 and Jh3 as baits.