The RAG1 and RAG2 gene products are Indispensable for activating somatic rearrangement of antlgen recep tor gene segments. The two proteins form a stable complex in primary thymocytes as well as when expressed In adherent cells. In both cell types, most cells localize RAG proteins at the periphery of the nucleus. However, when over-expressed in flbroblast cells, RAG1 is found largely in the nucleolus. Nucleolar localization of RAG1 is mediated by several domains containing stretches of basic amino acids, Indicating that RAG1 has affinity for RNA or ssDNA. The RAG1 lnteracting proteins SRPl and Rchl directly bind to the nuclear locallxatlon signals of RAGl, which mediate the nuclear and nucleolar translocation of the protein. RAG1 appears to have a binary structure, each half containing multlple regions that can act as NLSs, blndlng sites for the SRPlIRchl family, and RNA binding domains.

In the developing immune system, diversity of the antigen receptors, immunoglobulin, and T cell receptor (TCR) is generated by somatic rearrangement of gene segments in a site-specific process termed variable (diverse) joining (V [D] J) recombination (Tonegawa, 1983; Alt et al., 1987). This process is directed by highly conserved DNA recombination signal sequences (RSS) and executed by both ubiquitous and lymphoid-specific proteins (for review see Lewis and Gellert, 1989; Lieber, 1991; Schatz et al., 1992). Current models of V (D) J recombination are based mainly on the identification of V (D) J recombination intermediates (Roth et al., 1992; van Gent et al., 1995). Evidence for the involvement of ubiquitous activities stems from the analysis of the mutant nonlymphoid cell lines deficient in both V (D) J recombination and DNA repair (Kemp et al., 1984; Whitmore et al., 1989; Fulop and Philips, 1990; Hendrickson et al., 1991; Pergola et al., 1993; Taccioli et al.,