Temporal and spatial regulation of V(D)J recombination: Interactions of extrinsic factors with the RAG complex

In the course of lymphoid development, V(D)J recombination is subject to stringent locus-specific and temporal regulation. These constraints are ultimately responsible for several features peculiar to lymphoid development, including the lineage specificity of antigen receptor assembly, allelic exclusion and receptor editing. Inaddition, cell cycle phase-dependent regulation of V(D)J recombinase activity ensures that DNA rearrangement is completed by the appropriate mechanism of DNA repair. Regulation of V(D)J recombination involves interactions between the V(D)J recombinase-a heteromeric complex consisting of RAG-1 and RAG-2 subunits-and macromolecular assemblies extrinsic to the recombinase. This chapter will focus on those features of the recombinase it self-and in particular the RAG-2 subunit that interact with extrinsic factors to establish patterns of temporal control and locus specificity in developing lymphocytes.