Helicase processivity and not the unwinding velocity exhibits universal increase with force

TL;DR

This study presents a unified model showing that helicase processivity universally increases with force, unlike unwinding velocity, which varies among helicases, and suggests biological implications of this force-dependent processivity.

Contribution

The paper generalizes a model of helicase unwinding to explain force effects, predicting universal processivity increase and differentiating it from velocity responses.

Findings

Unwinding processivity universally increases with force across helicases.

Unwinding velocity response to force varies among different helicases.

The model explains the role of base pair disruption mechanisms in force sensitivity.

Abstract

Helicases, involved in a number of cellular functions, are motors that translocate along singlestranded nucleic acid and couple the motion to unwinding double-strands of a duplex nucleic acid. The junction between double and single strands creates a barrier to the movement of the helicase, which can be manipulated in vitro by applying mechanical forces directly on the nucleic acid strands. Single molecule experiments have demonstrated that the unwinding velocities of some helicases increase dramatically with increase in the external force, while others show little response. In contrast, the unwinding processivity always increases when the force increases. The differing responses of the unwinding velocity and processivity to force has lacked explanation. By generalizing a previous model of processive unwinding by helicases, we provide a unified framework for understanding the dependence of velocity and processivity on force and the nucleic acid sequence. We predict that the sensitivity of unwinding processivity to external force is a universal feature that should be observed in all helicases. Our prediction is illustrated using T7 and NS3 helicases as case studies. Interestingly, the increase in unwinding processivity with force depends on whether the helicase forces base pair opening by direct interaction or if such a disruption occurs spontaneously due to thermal uctuations. Based on the theoretical results, we propose that proteins like single-strand binding proteins associated with helicases in the replisome, may have co-evolved with helicases to increase the unwinding processivity even if the velocity remains unaffected.