Effect of supercoiling on the juxtaposition and relative orientation of DNA sites

There are many proteins that interact simultaneously with two or more DNA sites that are separated along the DNA contour. These sites must be brought close together to form productive complexes with the proteins. We used Monte Carlo simulation of supercoiled DNA conformations to study the effect of supercoiling and DNA length on the juxtaposition of DNA sites, the angle between them, and the branching of the interwound superhelix. Branching decreases the probability of juxtaposition of two DNA sites but increases the probability of juxtaposition of three sites at branch points. We found that the number of superhelix branches increases linearly with the length of DNA from 3 to 20 kb. The simulations showed that for all contour distances between two sites, the juxtaposition probability in supercoiled DNA is two orders of magnitude higher than in relaxed DNA. Supercoiling also results in a strong asymmetry of the angular distribution of juxtaposed sites. The effect of supercoiling on site-specific recombination and the introduction of supercoils by DNA gyrase is discussed in the context of the simulation results.