We work on the rearrangement of immunoglobulin and T-cell receptor genes, which is essential for the development of lymphoid cells. This process, known as V(D)J recombination, is unique in sharing some properties with site-specific recombination and with the repair of radiation damage to DNA. Our aim is to understand V(D)J recombination as thoroughly as possible, and then apply this knowledge to the immune system. We showed that recombination begins with site-specific DNA breaks, which can be made by the isolated RAG1 and RAG2 proteins, and that a DNA hairpin is produced on one side of each break. This reaction shares many properties with mobile genetic elements called transposons. We are interested in the potential role of transposition in causing chromosomal translocations of the types found in leukemia and lymphomas. We are also learning about covalent modifications of RAG1 by auto-ubiquitylation and by phosphorylation.