COMPLEMENTATION OF V(D)J RECOMBINATION DEFICIENCY IN RAG-1(- -) B-CELLS REVEALS A REQUIREMENT FOR NOVEL ELEMENTS IN THE N-TERMINUS OF RAG-1/

RAG-1 is an essential component of the site-specific V(D)J recombinase . A new assay system has revealed a significant contribution of the ca talytically dispensible N-terminal region of RAG-1 to recombination ac tivity. The foundation for this system is an Abelson virus-transformed cell line derived from RAG-1(-/-) mice that is dependent on the intro duction of exogenous RAG-1 for rearrangement of either plasmid substra tes or the endogenous immunoglobulin loci. Use of this line demonstrat es that conserved and novel cysteine-containing elements in the N-term inal region are required for full RAG-1 activity when recombination ac tivity is in a RAG-1 dose-responsive range. Our data suggest that the RAG-1 N-terminus enhances the formation of an active recombination com plex that facilitates the rearrangement process.