Our work is focused on the molecular mechanisms by which transposable elements move. These elements are discrete pieces of DNA that can move between many different insertion sites. They are present in virtually all organisms and contribute to both genome structure and function. (Hear a talk by Nancy about transposable elements)

     Despite the essential role of DNA in maintaining accurate genetic information, this molecule displays a surprising degree of plasticity. DNA rearrangements—the reorganization of DNA sequences by breakage, translocation, and rejoining reactions—mediate a wide variety of fundamental cellular processes. DNA rearrangements play an important role in the acquisition of new genetic elements such as viruses, in the control of gene expression during development, and in the repair of damaged DNA.

     We are particularly interested in the type of recombination called transposition. In this reaction, a discrete DNA segment moves from one donor position and inserts into another, non-homologous target site. An important consequence of transposon insertion is that information encoded by the transposon becomes stably linked with the target DNA.

     Transposable elements can have profound effects on genome structure and function. These elements have been identified in a wide variety of organisms. Indeed, the recent sequencing of the human genome has surprisingly revealed that about one half of the human genome is composed of DNA sequences related to transposable elements. Transposition can have considerable effect on the expression of genes encoded in the target DNA. For example, transposon insertion into a gene will likely inactivate that gene; transposon insertion into DNA sequences that control the expression of nearby genes may inactivate or activate those genes. Probably because of its potential for profound influence on the target DNA, transposition is highly regulated.

     Our research is focused on understanding several different transposons. One element, Tn7, is found in bacteria and displays unusual target selectivity. (Hear a talk by Nancy about "Tn7: a Smarter Transposon") Most transposable elements display only modest site selectivity, inserting into many different target sites. By contrast Tn7 inserts into a single specific site in the chromosomes of many bacteria. In Escherichia coli, this special site is called attTn7. When attTn7 is unavailable, Tn7 resembles most other transposable elements, inserting at low frequency into many different target sites. The Tn7 transposase is a member of the Retroviral Integrase superfamily.

     The other elements we study, Hermes and Tfo1, are members of the hAT superfamily which has many relatives in fungi, plants and animals. Notably, there are hAT elements that can transpose in vertebrates and there also appear to be intact hAT elements in the human genome. As judged by the lack of any obvious sequence similarity, hAT family transposases are unrelated to those of the Retroviral Integrase Superfamily. We are studying Hermes, an element found in Drosophila, and Tfo1, an element found in fungi.