RAG-1 and RAG-2, adjacent genes that synergistically activate V(D)J recombination.
The vast repertoire of immunoglobulins and T cell receptors is generated, in part, by V(D)J recombination, a series of genomic rearrangements that occur specifically in developing lymphocytes. The recombination activating gene, RAG-1, which is a gene expressed exclusively in maturing lymphoid cells, was previously isolated. RAG-1 inefficiently induced V(D)J recombinase activity when transfected into fibroblasts, but cotransfection with an adjacent gene, RAG-2, has resulted in at least a 1000-fold increase in the frequency of recombination. The 2.1-kilobase RAG-2 complementary DNA encodes a putative protein of 527 amino acids whose sequence is unrelated to that of RAG-1. Like RAG-1, RAG-2 is conserved between species that carry out V(D)J recombination, and its expression pattern correlates precisely with that of V(D)J recombinase activity. In addition to being located just 8 kilobases apart, these convergently transcribed genes are unusual in that most, if not all, of their coding and 3' untranslated sequences are contained in single exons. RAG-1 and RAG-2 might activate the expression of the V(D)J recombinase but, more likely, they directly participate in the recombination reaction.
Oettinger
M A
MA
Whitehead Institute for Biomedical Research, Cambridge, MA 02142.
Schatz
D G
DG
Gorka
C
C
Baltimore
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D
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D005075:Biological Evolution; D002417:Cattle; D002460:Cell Line; D002645:Chickens; D006224:Cricetinae; D004247:DNA / Q000235:genetics*; D004254:DNA Nucleotidyltransferases / Q000235:genetics*; D004268:DNA-Binding Proteins; D004285:Dogs; D005260:Female; D015322:Gene Rearrangement, B-Lymphocyte; D015329:Gene Rearrangement, T-Lymphocyte; D018398:Homeodomain Proteins; D006801:Humans; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D005810:Multigene Family; D009687:Nuclear Proteins; D009693:Nucleic Acid Hybridization; D009893:Opossums; D011506:Proteins / Q000235:genetics*; D011817:Rabbits; D011995:Recombination, Genetic / Q000235:genetics*; D015183:Restriction Mapping; D014162:Transfection; D014426:Turtles; D045567:VDJ Recombinases
D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D011506:Proteins; C499309:RAG2 protein, Oryctolagus cuniculus; C499311:RAG2 protein, human; C499308:Rag2 protein, mouse; C064655:V(D)J recombination activating protein 2; C064658:RAG-1 protein; D004247:DNA; D004254:DNA Nucleotidyltransferases; D045567:VDJ Recombinases