Processivity, velocity and universal characteristics of nucleic acid unwinding by helicases

Abstract

AbstractHelicases that act as motors and unwind double stranded nucleic acids are broadly classified as either active or passive, depending on whether or not they directly destabilize the double strand. By using this description in a mathematical framework, we derive analytic expressions for the velocity and run-length of a general model of finitely processive helicases. We show that, in contrast to the helicase unwinding velocity, the processivity exhibits a universal increase in response to external force. We use our results to analyze velocity and processivity data from single molecule experiments on the superfamily-4 ring helicase T7, and establish quantitatively that T7 is a weakly active helicase. We predict that compared to single-strand translocation, there is almost a two orders-of-magnitude increase in the back-stepping probability of T7 while unwinding double-stranded DNA. Our quantitative analysis of T7 suggests that the tendency of helicases to take frequent back-steps may be more common than previously anticipated, as was recently shown for the XPD helicase. Finally, our results suggest the intriguing possibility of a single underlying physical principle governing the experimentally observed increase in unwinding efficiencies of helicases in the presence of force, oligomerization or partner proteins like single strand binding proteins. The clear implication is that helicases may have evolved to maximize processivity rather than speed.