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Asymmetric DDE (D35E)-like sequences in the RAG proteins: implications for V(D)J recombination and retroviral
D H Dreyfus1, J F Jones, E W Gelfand
1Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO 80206, USA.
Abstract:
Experimental evidence suggests that the mechanism of vertebrate V(D)J recombination catalyzed by the vertebrate RAG proteins is similar to both retroviral integration and the transposition of IS630/Tc1-family transposons. The mechanism of both retroviral integration and IS630/Tc1 element transposition is well characterized and utilizes a functional metal ion binding site termed the DDE (or D35E) motif. We have previously identified a DDE-like region 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 retroviral pathogenesis in cells in which both the RAG proteins and retroviral integrase are co-expressed.
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