Helicases, involved in a number of cellular functions, are motors thattranslocate along singlestranded nucleic acid and couple the motion tounwinding double-strands of a duplex nucleic acid. The junction between doubleand single strands creates a barrier to the movement of the helicase, which canbe manipulated in vitro by applying mechanical forces directly on the nucleicacid strands. Single molecule experiments have demonstrated that the unwindingvelocities of some helicases increase dramatically with increase in theexternal force, while others show little response. In contrast, the unwindingprocessivity always increases when the force increases. The differing responsesof the unwinding velocity and processivity to force has lacked explanation. Bygeneralizing a previous model of processive unwinding by helicases, we providea unified framework for understanding the dependence of velocity andprocessivity on force and the nucleic acid sequence. We predict that thesensitivity of unwinding processivity to external force is a universal featurethat should be observed in all helicases. Our prediction is illustrated usingT7 and NS3 helicases as case studies. Interestingly, the increase in unwindingprocessivity with force depends on whether the helicase forces base pairopening by direct interaction or if such a disruption occurs spontaneously dueto thermal uctuations. Based on the theoretical results, we propose thatproteins like single-strand binding proteins associated with helicases in thereplisome, may have co-evolved with helicases to increase the unwindingprocessivity even if the velocity remains unaffected.
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