SPECIFICITY IN V(D)J RECOMBINATION - NEW LESSONS FROM BIOCHEMISTRY AND GENETICS

Recent in vitro work on V(D)J recombination has helped to clarify its mechanism. The first stage of the reaction, which can be reproduced wi th the purified RAG1 and RAG2 proteins, is a site-specific cleavage th at generates the same broken DNA species found in vivo. The cleavage r eaction is closely related to known types of transpositional recombina tion, such as that of HIV integrase. All the site specificity of V(D)J recombination, including the 12/23 rule, is determined by the RAG pro teins. The later steps largely overlap with the repair of radiation-in duced DNA double-strand breaks, as indicated by the identity of severa l newly characterized factors involved in repair. These developments o pen the way for a thorough biochemical study of V(D)J recombination.