(89g) The Effect of Nucleoid Associated Proteins on DNA Supercoiling

DNA compaction is critical in order for a long DNA strand to fit into a much smaller cell. This can be done in a number of ways including looping, compartment segregation, and supercoiling. The latter occurs when DNA is torsionally stressed and forms large-scale writhed structures by wrapping around itself to relieve this stress. In prokaryotic cells, nucleoid associated proteins (NAPs) play an important role in DNA organization and compaction by manipulating the shape and structure of the DNA. These NAPs act by bending or twisting DNA at the local scale, and we hypothesize that these local effects strongly impact the stability and structure of DNA supercoils.

We use a combination of coarse-grained simulation of NAPs and DNA and theory to investigate the effect that these proteins have on DNA supercoiling behavior. These proteins are preferentially bound to a bent DNA site via the binding and unbinding energy landscape. Additionally, these proteins change the local equilibrium angle upon binding, creating localized kinks in the DNA strand. We are able to capture experimental observations with our coarse-grained model. We can take this information to inform a theory that accounts for the effect that proteins have on the supercoiled system, such as the extension behavior, bending energy, and excluded volume that are dependent on concentration and force.