  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.
