The long-term goals of the proposed research project are to understand the molecular basis of and regulation of sequence specific protein-DNA recognition reactions leading to transposition. This will be pursued by studying the IS50/Tn5 transposition system. Transposable elements, such as IS50/Tn5, are genetic entities which can catalyze numerous types of genome rearrangements. They are thought to have been important in evolution and can lead to somatic cell mutations such as those associated with oncogenesis. Genetic and biochemical approaches will be used to analyze the interaction of IS50/Tn5 transposase with its target DNA sequences, the regulation of transposase activity by its inhibitor and the role of host proteins in the transposition process.