Difference Topology Analysis of Chirality and Geometry of Site-specific Recombination

University Of Texas At Austin, Austin TX

Investigators

Abstract

Intellectual Merit. Genomes undergo several types of rearrangements as part of normal cell growth, development and differentiation. Such DNA rearrangements fall into several categories, including homologous recombination, site-specific recombination, DNA transposition, and retro-transposition. These rearrangements proceed in a highly orderly and regulated manner instituted by high-order interactions of proteins with cognate DNA sequences as well as interactions among the proteins themselves. Proper action of site-specific recombinases requires proper geometry of the DNA dictated by two features: a) chirality, the handedness (right or left) in which DNA sites come together during a particular reaction, and b) alignment of the DNA molecules at the recombination site (parallel vs. anti-parallel). This project will use difference topology analysis to address two major questions about the mechanism of action of tyrosine family recombinases. Is there a defined chirality to the interaction of target sites? And how does the DNA sequence of recombination sites affect alignment of the target sites? The results of these studies will yield important insights with potential applications to genome engineering and biotechnology. Broader Impacts. The project will provide interdisciplinary training opportunities at the interface of mathematics and biology for a postdoctoral fellow, a graduate student and undergraduates. In addition, this interdisciplinary focus will be featured in classroom activities for graduate and undergraduate courses and in presentations for the lay public.