Definition of Ku-interacting domains in RAG1 and RAG2 proteins in V(D)J recombination

Abstract

V(D)J recombination is a process that generates the diversity of the immune repertoire against foreign antigens. During B and T cell development, genes encoding immunoglobulins (Ig) and T cell receptors (TCR) variable region are somatically assembled by selective V (variable), D (diversity) and J (joining) segments pre-existing in the germline. Recombination-activating genes 1 and 2 (RAG1/RAG2), the lymphocyte-specific factors, initiate V(D)J recombination by nicking at the border the heptamer sequence of RSS (recombination signal sequence) and generate four DNA double stranded breaks (DSB) in the cleavage step. After cleavage, RAG1/RAG2 complex are still bound to the DNA ends. In the joining step, DNA breaks are processed and rejoined by non-homologous end joining apparatus, which includes Ku70/Ku80, DNA-PKcs, Artemis, XRCC4 and DNA ligase IV. However, how the cleavage step is linked to the joining step is not yet known. My results suggest that a physical interaction between RAG1/2 and Ku antigen may help coordinate the cleavage stage of V(D)J with the non homologous DNA end rejoining of the mature sequences. (Abstract shortened by UMI.)