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RAG-1 mutations that affect the target specificity of V(D)j recombination: a possible direct role of RAG-1 in site
M J Sadofsky1, J E Hesse, D C van Gent
1Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Bethesda, Maryland 20892, USA.
Abstract:
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 particular mutation in RAG-1 affects recombination by altering the specificity of target sequence usage. Recombination mediated by wild-type RAG-1 is tolerant of a wide range of coding sequences adjacent to the recombination signal. With the mutant RAG-1, recombination is much more demanding; efficient recombination is only found when particular dinucleotides are adjacent to the signal sequence heptamer. The mutant is also more sensitive than wild-type RAG-1 to certain alterations within the signal sequence. We suggest that the RAG-1 protein may interact physically with the target DNA at the coding-signal sequence border.