V(D)J recombination: site-specific cleavage and repair.
V(D)J recombination is a site-specific gene rearrangement process that contributes to the diversity of antigen receptor repertoires. Two lymphoid-specific proteins, RAG1 and RAG2, initiate this process at two recombination signal 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 border between signal and coding sequence, and carries out a transesterification reaction, resulting in the production of a hairpin structure at the coding 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 signal binding and cleavage. After DNA cleavage by the RAG complex, the broken DNA ends are rejoined by the coordinated action of DNA double-strand break repair proteins as well as the RAG complex. The junctional variability resulting from imprecise joining of the coding sequences contributes additional diversity to the antigen receptors.
Kim
D R
DR
Department of Molecular Biology, Massachusetts General Hospital, Harvard Medical School, Boston 02114, USA.
Park
S J
SJ
Oettinger
M A
MA
D000818:Animals; D001665:Binding Sites; D004254:DNA Nucleotidyltransferases / Q000378:metabolism; D004260:DNA Repair; D004251:DNA Transposable Elements; D015321:Gene Rearrangement; D006609:High Mobility Group Proteins / Q000502:physiology; D007128:Immunoglobulin Fragments / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008957:Models, Genetic; D011995:Recombination, Genetic; D012045:Regulatory Sequences, Nucleic Acid; D045567:VDJ Recombinases
D004251:DNA Transposable Elements; D006609:High Mobility Group Proteins; D007128:Immunoglobulin Fragments; D004254:DNA Nucleotidyltransferases; D045567:VDJ Recombinases