Effect of DNA Superhelicity and Bound Proteins on Mechanistic Aspects of
the Hin-mediated and Fis-enhanced Inversion
Using a recently developed inhomogeneous, macroscopic model for long DNA bound
to pro-teins, we examine topological and geometric aspects of DNA/protein
structures and dynamics on various stages of the Hin inversion pathway.
This biological reaction involves exchange of DNA in a synaptic complex
which brings together several DNA sites bound to Hin dimers as well as Fis
enhancers. Brownian dynamics simulations in the millisecond timescale
allow us to follow and an-alyze the DNA/protein dynamics trajectories and
to examine the effects of DNA superhelicity and protein binding on various
reaction steps. Analysis of the generated kinetic pathways helps explain
mechanistic aspects regarding the process by which two or three protein-bound
DNA sites come to close spatial proximity and show that how topological
selectivity (two trapped supercoils), enhancer binding, and properties
of supercoiled DNA play critical roles in regulating the inversion reaction.
Specifically, a critical amount of DNA superhelicity
leads to an optimal interplay for the first reaction step two-site
juxtaposition between large-scale random rearrangements of Hin-bound DNA
and local slithering within branches of plectonemes. The three-site
juxtaposi-tion, the second step, is significantly accelerated by the
presence of an enhancer protein which, due to severe local bending,
also alters juxtaposition mechanisms, especially for superhelical density
magnitude greater than around 0.04.
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