Research advances and prospects of initiation of V(D)J recombination

The initiation of V(D)J recombination by the proteins encoded by the recombination activating genes RAG1 and RAG2 is carefully orchestrated to ensure that antigen receptor gene assembly occurs in the appropriate cell lineage and in the proper developmental order. Here we review the recent advances in the mechanisms of DNA binding and cleavage by the RAG proteins in antigen receptor genes. These advances suggest novel mechanisms for both the targeting and the mistargeting of V(D)J recombination, with implications for how the reaction contributes to genome instability and lymphoid malignancy.