The bounty of RAGs: recombination signal complexes and reaction outcomes

• Published in: Immunological reviews Vol. 200; no. 1; pp. 90 - 114
• Main Author: Swanson, Patrick C.
• Format: Journal Article
• Language: English
• Published: Oxford, UK; Malden, USA Munksgaard International Publishers 01-08-2004
• Subjects: Animals; Base Sequence; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Gene Rearrangement, B-Lymphocyte; Gene Rearrangement, T-Lymphocyte; HMGB1 Protein - genetics; HMGB1 Protein - metabolism; HMGB2 Protein - genetics; HMGB2 Protein - metabolism; Homeodomain Proteins - genetics; Homeodomain Proteins - metabolism; Humans; Molecular Sequence Data; Nuclear Proteins; Protein Sorting Signals; VDJ Recombinases - physiology
• ISSN: 0105-2896; 1600-065X
• DOI: 10.1111/j.0105-2896.2004.00159.x

V(D)J recombination is a form of site‐specific DNA rearrangement through which antigen receptor genes are assembled. This process involves the breakage and reunion of DNA mediated by two lymphoid cell‐specific proteins, recombination activating genes RAG‐1 and RAG‐2, and ubiquitously expressed architectural DNA‐binding proteins and DNA‐repair factors. Here I review the progress toward understanding the composition, assembly, organization, and activity of the protein‐DNA complexes that support the initiation of V(D)J recombination, as well as the molecular basis for the sequence‐specific recognition of recombination signal sequences (RSSs) that are the targets of the RAG proteins. Parallels are drawn between V(D)J recombination and Tn5/Tn10 transposition with respect to the reactions, the proteins, and the protein‐DNA complexes involved in these processes. I also consider the relative roles of the different sequence elements within the RSS in recognition, cleavage, and post‐cleavage events. Finally, I discuss alternative DNA transactions mediated by the V(D)J recombinase, the protein‐DNA complexes that support them, and factors and forces that control them.