Immunoglobulin gene rearrangement. Proteins RAG1 and RAG2 bind to RSS (recombination signal sequences) and cleave one DNA strand between the RSS and the V (or J) segments that are to be joined. The liberated 3′ hydroxyl acts as a nucleophile, attacking a phosphodiester bond in the other strand to create a double-strand break. The resulting hairpins on the V and J segments are cleaved, and the ends are covalently linked by a complex of proteins specialized for end-joining repair of double-strand breaks, as described in Chapter 13. The steps in the generation of the double-strand break, catalyzed by RAG1 and RAG2, are chemically related to steps in transposition reactions.