David Gilliam Schatz

With Baltimore, codiscovered that V(D)J recombination activity could be generated in nonlymphoid cells by genomic DNA transfection. With Oettinger, identified and characterized the Recombination Activating Genes RAG1 and RAG2, which encode the vital components of the V(D)J recombination machinery. Since then, provided important insights into the mechanism of V(D)J recombination, including creation of the first cell-free system for properly regulated DNA cleavage, the crystal structure of a RAG DNA binding domain, and identification of a synaptic complex formed by the RAG proteins. With Gellert, codiscovered the ability of RAG1/2 to perform DNA transposition, with implications for our understanding of the evolution of the adaptive immune system. Uncovered fundamental parameters regulating V(D)J recombination, demonstrating that RAG proteins orchestrate the reaction from within focal recombination centers at antigen receptor loci and revealing several distinct pathways for the recruitment of RAG1/2 to chromatin.  Recently, identified events underlying the "molecular domestication" of the RAG transposon to yield the RAG recombinase, and provided detailed structural insights into transposases evolutionarily related to RAG.