Chapter 12 - A General Model of DNA Unwinding by Monomeric Helicases

Abstract

It has been shown experimentally that during nucleic acids (NA) unwinding by monomeric helicases some, such as RecQ and HCV NS3, exhibit rare backward steps while others, such as XPD, show frequent backward steps. Here, we present a general model of NA unwinding by the monomeric helicases based on the available structural data. With the model we explain why XPD exhibits frequent backsteps while RecQ and HCV NS3 show rare backsteps. We theoretically study the NA unwinding velocity, probability of –1-bp step, mean dwell time, etc., for XPD under variations of ATP concentration and external force applied to the two complementary termini of the NA hairpin to unzip it. We also theoretically study the NA unwinding velocity of RecQ and HCV NS3 under variation of external force. The theoretical data reproduce quantitatively the available single-molecule experimental data. The theoretical data show that the NA unwinding velocity of XPD is sensitively dependent on the external force, in contrast to RecQ and HCV NS3 that show insensitive force-dependence of the NA unwinding velocity, explaining the available experimental data showing that RecQ is an “optimally active” helicase while XPD is a “partially active” one. Moreover, the DNA unwinding dynamics of different helicases under variation of the external force is studied.