rag-1 and rag-2: Biochemistry and Protein Interactions

Abstract

The process of V(D)J recombination is the defining characteristic of lymphocyte development. This site-specific recombination reaction assembles the genes that encode immunoglobulin (lg) and T cell receptor proteins, and in many species is the source of much of the diversity in these gene products. The reaction is complex and almost certainly requires the coordinated activity of a large number of proteins. Most components of the V(D)J recombination enzymatic machinery (hereafter referred to as the V(D)J recombinase) are ubiquitously expressed, with only three lymphocyte-specific factors thus far identified: the products of the recombination activating genes (RAG-1 and RAG-2), and terminal deoxynucleotidyl transferase (TdT). TdT is not required for V(D)J recombination, but when present it functions to add nongermline-encoded nucleotides (N regions) to coding junctions and thereby greatly increases the diversity of the products of the reaction. The rag-1 and rag-2 proteins are central to the process of V(D)J recombination, and their biochemical properties and protein-protein interactions are the focus of this chapter.