V(D)J recombination: Site-specific cleavage and repair

V(D)J recombination is a site-specific gene rearrangement process that cont ributes to the diversity of antigen receptor repertoires, Two lymphoid-spec ific proteins, RAG1 and RAG2, initiate this process at two recombination si gnal sequences. Due to the recent development of an in vitro assay for V(D) J cleavage, the mechanism of cleavage has been elucidated clearly. The RAG complex recognizes a recombination signal sequence, makes a nick at the bor der between signal and coding sequence, and carries out a transesterificati on reaction, resulting in the production of a hairpin structure at the codi ng sequence and DNA double-strand breaks at the signal ends. RAG1 possesses the active site of the V(D)J recombinase although RAG2 is essential for si gnal binding and cleavage. After DNA cleavage by the RAG complex, the broke n DNA ends are rejoined by the coordinated action of DNA double-strand brea k repair proteins as well as the RAG complex. The junctional variability re sulting from imprecise joining of the coding sequences contributes addition al diversity to the antigen receptors.