Similarities between initiation of V(D)J recombination and retroviral integration.
In the first step of V(D)J recombination, the RAG1 and RAG2 proteins cleave DNA between a signal sequence and the adjacent coding sequence, generating a blunt signal end and a coding end with a closed hairpin structure. These hairpins are intermediates leading to the formation of assembled antigen receptor genes. It is shown here that the hairpins are formed by a chemical mechanism of direct trans-esterification, very similar to the early steps of transpositional recombination and retroviral integration. A minor variation in the reaction is sufficient to divert the process from transposition to hairpin formation.
van Gent
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Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0540, USA.
Mizuuchi
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K
Gellert
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M
D001483:Base Sequence; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D004254:DNA Nucleotidyltransferases / Q000378:metabolism; D004251:DNA Transposable Elements; D004268:DNA-Binding Proteins; D004951:Esterification; D015321:Gene Rearrangement; D015329:Gene Rearrangement, T-Lymphocyte; D005803:Genes, Immunoglobulin; D006678:HIV / Q000235:genetics*; D018398:Homeodomain Proteins; D019426:Integrases; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D011506:Proteins / Q000378:metabolism; D045522:Recombinases; D011995:Recombination, Genetic; D013873:Thionucleotides / Q000378:metabolism; D045567:VDJ Recombinases; D016662:Virus Integration
D004251:DNA Transposable Elements; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D011506:Proteins; D045522:Recombinases; D013873:Thionucleotides; C064655:V(D)J recombination activating protein 2; C064658:RAG-1 protein; D004247:DNA; D004254:DNA Nucleotidyltransferases; D019426:Integrases; D045567:VDJ Recombinases; C115006:integron integrase IntI1