Remote Control Of Dna-Acting Enzymes By Molecular Boundary Conditions

The rate of action of an enzyme at a point along a long DNA molecule is usually assumed to be determined by the local properties of that region of the nucleic acid chain such as its sequence, flexibility, and molecular stress. Here we show that enzymes that relax DNA torsional stress display rates which strongly depend on how the distant ends of the molecule are constrained: experiments with different size colloidal particles tethered to the end of 10 kb DNAs reveal enzyme rates that are inversely correlated with particle drag coefficient. This effect can be understood in terms of the coupling between molecule extension and local molecular stresses: the rate of bead thermal motion controls the rate at which transition states are visited in the middle of a long DNA. Torsional stress is not a requirement for this effect. Importantly, some enzymes show rates unaffected by bead size. Our results reveal a new mechanism through which variation in chromosome domain architecture, and more generally, large-scale architecture of large thermally fluctuating substrates, can control enzyme rates.