DNA transposition by the RAG1 and RAG2 proteins: a possible source of oncogenic translocations.
The RAG1 and RAG2 proteins are known to initiate V(D)J recombination by making a double-strand break between the recombination signal sequence (RSS) and the neighboring coding DNA. We show that these proteins can also drive the coupled insertion of cleaved recombination signals into new DNA sites in a transpositional reaction. This RAG-mediated DNA transfer provides strong evidence for the evolution of the V(D)J recombination system from an ancient mobile DNA element and suggests that repeated transposition may have promoted the expansion of the antigen receptor loci. The inappropriate diversion of V(D)J rearrangement to a transpositional pathway may also help to explain certain types of DNA translocation associated with lymphatic tumors.
Hiom
K
K
Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0540, USA.
Melek
M
M
Gellert
M
M
D004247:DNA / Q000378:metabolism*; D004254:DNA Nucleotidyltransferases / Q000378:metabolism; D004251:DNA Transposable Elements; D004268:DNA-Binding Proteins / Q000378:metabolism*; D019143:Evolution, Molecular; D015329:Gene Rearrangement, T-Lymphocyte; D018398:Homeodomain Proteins / Q000378:metabolism*; D008223:Lymphoma / Q000209:etiology; D008957:Models, Genetic; D009713:Nucleotidyltransferases / Q000378:metabolism*; D009857:Oncogenes; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D011995:Recombination, Genetic; D014178:Translocation, Genetic; D019895:Transposases / Q000378:metabolism*; D045567:VDJ Recombinases
D004251:DNA Transposable Elements; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D011948:Receptors, Antigen, T-Cell; C064655:V(D)J recombination activating protein 2; C064658:RAG-1 protein; D004247:DNA; D004254:DNA Nucleotidyltransferases; D009713:Nucleotidyltransferases; D019895:Transposases; D045567:VDJ Recombinases