DNA handles bias force-dependent looping times

DNA loop formation is a key mechanism in gene regulation, and looping kinetics are sensitive to mechanical tension acting on the DNA.

In both single-molecule experiments and biological settings, this tension is typically transmitted through DNA segments flanking the looping region, rather than acting directly at the looping sites.

How this indirect force transmission affects the looping time has not been systematically investigated.

Using molecular dynamics simulations of a wormlike chain, we show that such flanking segments significantly steepen the force dependence of the looping time, an effect that is insensitive to their length once it exceeds the persistence length, and vanishes when the junction to the looping region is made flexible.

We develop an analytical framework that accounts for this effect through a force-dependent shift in the effective free energy landscape of the looping segment.

In the limit of small forces, this shift reduces to a zero-force equilibrium average, after which the entire force dependence of the looping time follows analytically.

Applying this framework using a coarse-grained DNA model that treats individual bases as rigid bodies, we obtain predictions in quantitative agreement with experimental looping data.

Our results demonstrate that the geometry of force transmission has a significant and predictable effect on looping kinetics, with direct implications for the interpretation of tension-dependent looping in both single-molecule experiments and gene regulatory contexts.