Dynamics of DNA unwinding by helicases with frequent backward steps

Abstract

XPD (Xeroderma pigmentosum complementation group D) is a prototypical 5′ – 3′ translocating DNA helicase that exhibits frequent backward steps during DNA unwinding. Here, we propose a model of DNA unwinding by XPD. With the model we explain why XPD exhibits frequent backsteps while other helicases show rare backsteps. We explain quantitatively the single-molecule data on probability of –1-bp step and mean dwell time of one step versus ATP concentration for XPD at fixed large external force applied to the ends of the DNA hairpin to unzip the hairpin. We study DNA unwinding velocity, probability of –1-bp step and mean dwell time of one step for XPD versus external force at various ATP concentrations. We compare DNA unwinding dynamics of the 5′ – 3′ helicase XPD with that of 3′ – 5′ helicase RecQ. Our results show that the DNA unwinding velocity of XPD is sensitively dependent on the external force, which is contrast to RecQ that shows insensitive dependence of DNA unwinding velocity on the external force, explaining the experimental data showing that RecQ is an “optimally active” helicase while XPD is a “partially active” helicase. The DNA unwinding dynamics of different helicases under the external force is also studied.