V(D)J recombination signal recognition: distinct, overlapping DNA-protein contacts in complexes containing RAG1 with and without RAG2.

Protein interactions with V(D)J recombination signal sequences (RSSs) were mapped in complexes containing RAG1 with (M1/2) or without (M1) RAG2. In both complexes, RAG interactions with the DNA backbone are biased toward one side of the helix; nonamer contacts resemble those of Hin with hixL. In the M1 complex, DNA contacts are centered on the nonamer. In the M1/2 complex, protein-RSS interactions extend through the spacer and into the nonamer-proximal portion of the heptamer. Chemical modifications near the heptamer-coding junction are overrepresented in the M1/2 complex, providing evidence for perturbation of DNA structure in this region. Thus, while RAG1 alone can bind the nonamer, RAG2 is required for heptamer occupancy.