RAG-1 and RAG-2, Adjacent Genes That Synergistically Activate V(D)J Recombination

• Published in: Science (American Association for the Advancement of Science) Vol. 248; no. 4962; pp. 1517 - 1523
• Main Authors: Oettinger, Marjorie A., Schatz, David G., Gorka, Carolyn, Baltimore, David
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for the Advancement of Science 22.06.1990; American Association for the Advancement of Science; The American Association for the Advancement of Science
• Subjects: Amino Acid Sequence; Animals; B lymphocytes; Base Sequence; Biological and medical sciences; Biological Evolution; Blood; Cattle; Cell Line; Cell lines; Chickens; Complementary DNA; Cricetinae; DNA; DNA - genetics; DNA Nucleotidyltransferases - genetics; DNA-Binding Proteins; Dogs; Female; Fibroblasts; Fundamental and applied biological sciences. Psychology; Gene Rearrangement, B-Lymphocyte; Gene Rearrangement, T-Lymphocyte; Generally accepted auditing standards; Genes; Genetics; Genic rearrangement. Recombination. Transposable element; Genomics; Homeodomain Proteins; Humans; Lymphocytes; Male; Medical research; Mice; Molecular and cellular biology; Molecular genetics; Molecular Sequence Data; Multigene Family; Nuclear Proteins; Nucleic Acid Hybridization; Opossums; Proteins - genetics; Rabbits; Recombination, Genetic - genetics; Research Article; Restriction Mapping; T lymphocytes; T-cell receptor; Transfection; Turtles; VDJ Recombinases; Vertebrata; Recombination; Mammalia; Complementary DNA; Mouse; Nucleotide sequence; Rodentia; Gene rearrangement; Primary structure; Activation; Molecular cloning; Aminoacid sequence
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.2360047

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.