RAG-1 MUTATIONS THAT AFFECT THE TARGET SPECIFICITY OF V(D)J RECOMBINATION - A POSSIBLE DIRECT ROLE OF RAG-1 IN SITE RECOGNITION

The RAG-1 protein plays an essential role in V(D)J recombination, but its exact function has not yet been defined. Here we report that a par ticular mutation in RAG-1 affects recombination by altering the specif icity of target sequence usage. Recombination mediated by wild-type RA G-1 is tolerant of a wide range of coding sequences adjacent to the re combination signal. With the mutant RAG-1, recombination is much more demanding; efficient recombination is only found when particular dinuc leotides are adjacent to the signal sequence heptamer. The mutant is a lso more sensitive than wild-type RAG-1 to certain alterations within the signal sequence. We suggest that the RAG-1 protein may interact ph ysically with the target DNA at the coding-signal sequence border.