RAG2 (V(D)J recombination-activating protein 2) is a core component of the RAG complex - a multiprotein complex that mediates the DNA cleavage phase during V(D)J recombination. V(D)J recombination assembles a diverse repertoire of immunoglobulin and T-cell receptor genes in developing B and T-lymphocytes through rearrangement of different V (variable), in some cases D (diversity) and J (joining) gene segments. DNA cleavage by the RAG complex occurs in 2 steps: 1) first a nick is introduced in the top strand immediately upstream of the heptamer, generating a 3'-hydroxyl group that can attack the phosphodiester bond on the opposite strand in a direct transesterification reaction, thereby creating 4 DNA ends. 2) hairpin coding ends and 2 blunt, 5'-phosphorylated ends are created. The chromatin structure plays an essential rold in the V(D)J recombination reactions and the presence of histone H3 trimethylated at 'Lys-4' (H3K4me3) stimulates both the nicking and hair pinning expressed on individual B-lymphocytes. The introduction of DNA breaks by the RAG complex on one immunoglobulin allele induces ATM-dependent repositioning of the other allele to pericentromeric heterochromatin. This prevents accessibility to the RAG complex and recombination of the second allele. In the RAG complex, RAG2 is not the catalytic component but is required for all known catalytic activities mediated by RAG1. Mutations affecting the gene can results in combined cellular and humoral immune defects with granulomas, severe combined immunodeficiency autosomal recessive T-cell-negative/B-cell-negative/NK-cell-positive, and Omenn syndrome.
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Protein Aliases: RAG 2; RAG-2; recombinase activating gene 2; recombination activating protein 2; V(D)J recombination-activating protein 2
Gene Aliases: RAG-2; RAG2