The bounty of RAGs: recombination signal complexes and reaction outcomes.
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.
Swanson
Patrick C
PC
Department of Medical Microbiology and Immunology, Creighton University Medical Center, Omaha, NE 68178, USA. pswanson@creighton.edu
D000818:Animals; D001483:Base Sequence; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015322:Gene Rearrangement, B-Lymphocyte; D015329:Gene Rearrangement, T-Lymphocyte; D024243:HMGB1 Protein / Q000235:genetics / Q000378:metabolism; D024261:HMGB2 Protein / Q000235:genetics / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D021382:Protein Sorting Signals; D045567:VDJ Recombinases / Q000502:physiology
D004268:DNA-Binding Proteins; D024243:HMGB1 Protein; D024261:HMGB2 Protein; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D021382:Protein Sorting Signals; C499311:RAG2 protein, human; C064655:V(D)J recombination activating protein 2; C064658:RAG-1 protein; D045567:VDJ Recombinases