title: Asymmetric DDE (D35E)-like sequences in the RAG proteins: implications for V(D)J recombination and retroviral pathogenesis.
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.
authors.affiliation: Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO 80206, USA.
authors.forename: D H
authors.initials: DH
authors.lastname: Dreyfus
authors.forename: J F
authors.initials: JF
authors.lastname: Jones
authors.forename: E W
authors.initials: EW
authors.lastname: Gelfand
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017124:Conserved Sequence; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D018398:Homeodomain Proteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008670:Metals / Q000378:metabolism*; D008954:Models, Biological; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D011995:Recombination, Genetic; D012190:Retroviridae / Q000472:pathogenicity*
chemical_list: D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D008670:Metals; D009687:Nuclear Proteins; C499311:RAG2 protein, human; C064655:V(D)J recombination activating protein 2; C064658:RAG-1 protein