Prediction of Target DNA Recognition By Transposons

Transposons which are also called transposable elements are short sequences of DNA that can move from one place to another in a genome by a cut and paste mechanism so called transposition. Transposition is mediated by a transposase, an enzyme encoded by the transposon. Transposases are classified to many families. Mos1 transposase belongs to one of these families - Tc1/mariner superfamily. Understanding how transposase interacts with target DNA might open up the possibility of developing gene therapy vectors that can integrate at different DNA sequences and might reveal a target for blocking transposition of bacterial transposons. With the information of Tc1/mariner superfamily and Mos1 transposase crystal structure which is solved by Julia Richardson, it allows us to predict the site at which target DNA is bound before strand transfer. In this project, I tried to predict the target DNA binding residues in two ways - sequence analysis and structure modeling. I have assembled a set of amino acid sequences related to that of Mos1 from the literature and from genome sequence data, and comparing the sequence of the putative target binding sites of each in order to find the highly conserved residues in the catalytic domain of Mos1. I have selected six transposase sequences to do structure modeling with the solved structure as template. With the information from combining sequences and models, I have tried to predict the residues responsible for DNA binding function. At the same time, there is a private transposase database built by David Finnegan which stores supplemental information of residues of particular transposases. I have developed a tool for researchers easy to visually link information in the database about particular residues in the Mos1 transposase, or any other transposases, with a graphical representation of its structure.