RAG-1 and RAG-2, adjacent genes that synergistically activate V(D)J recombination

Science. 1990 Jun 22;248(4962):1517-23. 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Biological Evolution
  • Cattle
  • Cell Line
  • Chickens
  • Cricetinae
  • DNA / genetics*
  • DNA Nucleotidyltransferases / genetics*
  • DNA-Binding Proteins*
  • Dogs
  • Female
  • Gene Rearrangement, B-Lymphocyte*
  • Gene Rearrangement, T-Lymphocyte*
  • Homeodomain Proteins*
  • Humans
  • Male
  • Mice
  • Molecular Sequence Data
  • Multigene Family*
  • Nuclear Proteins
  • Nucleic Acid Hybridization
  • Opossums
  • Proteins / genetics*
  • Rabbits
  • Recombination, Genetic / genetics*
  • Restriction Mapping
  • Transfection
  • Turtles
  • VDJ Recombinases


  • DNA-Binding Proteins
  • Homeodomain Proteins
  • Nuclear Proteins
  • Proteins
  • RAG2 protein, Oryctolagus cuniculus
  • RAG2 protein, human
  • Rag2 protein, mouse
  • V(D)J recombination activating protein 2
  • RAG-1 protein
  • DNA
  • DNA Nucleotidyltransferases
  • VDJ Recombinases

Associated data

  • GENBANK/M33828
  • GENBANK/M64796