Asymmetric DDE (D35E)-like sequences in the RAG proteins: implications forV(D)J recombination and retroviral pathogenesis

Experimental evidence suggests that the mechanism of vertebrate V(D)J recom bination catalyzed by the vertebrate RAG proteins is similar to both retrov iral integration and the transposition of IS630TTc1-family transposons. The mechanism of both retroviral integration and IS630TTc1 element transpositi on is well characterized and utilizes a functional metal ion binding site t ermed the DDE (or D35E) motif, We have previously identified a DDE-like reg ion in the RAG-2 protein and a similar region within the RAG-1 protein. In this work, we propose that interference between DDE-like regions in the RAG proteins and the DDE-site of the HIV integrase may be a mechanism of retro viral pathogenesis in cells in which both the RAG proteins and retroviral i ntegrase are co-expressed.