(638e) Role of Length-Scale Dependent DNA Flexibility in Protein Interactions

The proteins responsible for reading and packaging the genome must harness the full range of DNA mechanical properties, from bending a rigid DNA strand at short length scales to searching through a meandering, dynamic DNA chain at long length scales. We use the wormlike chain model as a simple description to study the fundamental physics involved at these different regimes. We will present our work on three questions concerning DNA biophysics. First, we look at the effective interaction between DNA bending proteins that arises from elastic stresses in the linker while the DNA is under external tension. Cooperative binding of proteins is required to assemble transcription factor complexes and to condense DNA into chromatin. We demonstrate that the elastic nature of the double helix generates a variable-range oscillatory coupling that may provide a versatile mechanism for tension-mediated regulation of cooperativity and aggregation. We then expand our analytical techniques into practical tools for extracting structural information from single-molecule trapping experiments, with application to nucleosome unwrapping and DNA gyrase mechanics. We consider the relative contributions of elastic bending and entropic fluctuations when measuring DNA kinking at low tensions. Finally, we study the effects of crowding and roadblocks on the competition of timescales for a transcription factor searching through the genome by a combination of one-dimensional sliding and three-dimensional hops.