Key Laboratory of Soft Matter Physics and Beijing National Laboratory for Condensed Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing 100190, China.
Math Biosci. 2017 Dec;294:33-45. doi: 10.1016/j.mbs.2017.10.004. Epub 2017 Oct 10.
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.
XPD（着色性干皮病互补组 D）是一种典型的 5' - 3' 移位 DNA 解旋酶，在 DNA 解旋过程中频繁出现后退步骤。在这里，我们提出了一种 XPD 解旋的模型。通过该模型，我们解释了为什么 XPD 频繁出现后退步骤，而其他解旋酶则很少出现后退步骤。我们定量解释了在固定施加于 DNA 发夹两端的大外力下，XPD 的单分子数据，即在固定施加于 DNA 发夹两端的大外力下，XPD 的 -1-bp 步概率和一步平均停留时间与 ATP 浓度的关系，用于解开发夹。我们研究了 XPD 与各种 ATP 浓度下的外力的 DNA 解旋速度、-1-bp 步概率和一步平均停留时间。我们比较了 5' - 3' 解旋酶 XPD 和 3' - 5' 解旋酶 RecQ 的 DNA 解旋动力学。我们的结果表明，XPD 的 DNA 解旋速度对外力敏感依赖，这与 RecQ 形成对比，RecQ 对外力的 DNA 解旋速度不敏感依赖，解释了实验数据表明 RecQ 是一种“最佳活性”解旋酶，而 XPD 是一种“部分活性”解旋酶。还研究了不同解旋酶在外力下的 DNA 解旋动力学。
