The RAG1 N-terminal region regulates the efficiency and pathways of synapsis for V(D)J recombination
Immunoglobulin and T cell receptor gene assembly depends on V(D)J recombination initiated by the RAG1-RAG2 recombinase. The RAG1 N-terminal region (NTR; aa 1-383) has been implicated in regulatory functions whose influence on V(D)J recombination and lymphocyte development in vivo are poorly understood. We generated mice in which RAG1 lacks ubiquitin ligase activity (P326G), the major site of autoubiquitination (K233R), or its first 215 residues (d215). While few abnormalities were detected in R1.K233R mice, R1.P326G mice exhibit multiple features indicative of reduced recombination efficiency including an increased Igk+:Igl+ B cell ratio and decreased recombination of Igh, Igk, Igl, 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 R1d215 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.
Keywords
Basic Immunology, MouseItem Type | Dataset |
---|---|
Capture method | Unknown |
Date | 8 September 2021 |
Language(s) of written materials | English |
Creator(s) |
Beilinson, HA |
LSHTM Faculty/Department | Faculty of Infectious and Tropical Diseases > Dept of Clinical Research |
Participating Institutions | London School of Hygiene & Tropical Medicine, London, United Kingdom |
Date Deposited | 08 Aug 2023 12:44 |
Last Modified | 10 Aug 2023 08:59 |
Publisher | immunoSEQ Analyze |
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- immunoSEQ Analyze (Online Data Resource)