U.S. Department of Health and Human Services
Research Summary/In Plain Language

Research Summary

Research Goal

Our goal is to understand the process of DNA transposition by crystallizing specific Hermes-DNA complexes at various stages of the transposition reaction.  We hope that by understanding how the Hermes protein catalyzes DNA breakage and re-joining reactions, we will gain insights into its mechanism and regulation, allowing us to optimize Hermes (and perhaps other eukaryotic transposases) for use as a genetic tool in eukaryotic cells.

Current Research

The basic research we are performing is aimed at understanding the various biochemical mechanisms by which discrete pieces of DNA move from one place in the genome to another.  This process is called DNA transposition.  In particular, we have been studying the eukaryotic transposon, Hermes, an active hAT transposon originally isolated from Musca domestica (the housefly).  We have obtained the crystal structure of the protein alone, in complex with its transposon ends, and hope to extend this work to the characterization of other steps in the transposition reaction.​

Applying our Research

We are interested in eukaryotic transposons, as they provide a valuable experimental tool to manipulate the genomes of eukaryotic cells. For example, they have been used as a way to eliminate genes selectively and to then observe the consequences. Alternatively, the introduction of specific genes is the conceptual foundation of gene therapy approaches to curing diseases. DNA transposition systems in current use in mammalian cells include the resurrected Sleeping Beauty transposon and piggyBac, which are not always ideal for their desired applications. We reasoned that x-ray structures of eukaryotic DNA transposases would provide important insights into their mechanisms and regulation.