Mechanism of V(D)J recombination

THe V(D)J recombination reaction can be separated into two fundamental operations: site specific cleavage and joining of broken ends. Much has been learned about the mechanisms of these steps in the past few years. Recent experiments have shown that cleavage is catalyzed by the RAG1 and RAG2 proteins and generates an asymmetric set of broken ends: hairpin coding ends and blunt signal ends. A cell free system capable of performing cleavages has been established, and detailed biochemical information about the reaction should accumulate rapidly. In vivo studies have provided insights into the regulation of cleavage. Recent experiments using artificial recombination substrates in cultured cells have shown that efficient cleavage requires a pair of RSS, one with a 12 nucleotide spacer and one with a 23 nucleotide spacer. Our understanding of the joining mechanism has also increased substantially, as several proteins involved in coding joint and signal joint formation (as well as in DSB repair) were recently identified.