Department of Physics, Indian Institute of Technology, Kanpur, 208016, India.
J Phys Condens Matter. 2013 Sep 18;25(37):374105. doi: 10.1088/0953-8984/25/37/374105. Epub 2013 Aug 15.
A DNA polymerase (DNAP) replicates a template DNA strand. It also exploits the template as the track for its own motor-like mechanical movement. In the polymerase mode it elongates the nascent DNA by one nucleotide in each step. However, whenever it commits an error by misincorporating an incorrect nucleotide, it can switch to an exonuclease mode. In the latter mode it excises the wrong nucleotide before switching back to its polymerase mode. We develop a stochastic kinetic model of DNA replication that mimics an in vitro experiment where single-stranded DNA, subjected to a mechanical tension F, is converted to double-stranded DNA by a single DNAP. The F-dependence of the average rate of replication, which depends on the rates of both polymerase and exonuclease activities of the DNAP, is in good qualitative agreement with the corresponding experimental results. We introduce nine novel distinct conditional dwell times of a DNAP. Using the method of first-passage times, we also derive the exact analytical expressions for the probability distributions of these conditional dwell times. The predicted F-dependences of these distributions are, in principle, accessible to single-molecule experiments.
DNA 聚合酶（DNAP）复制模板 DNA 链。它还利用模板作为自身马达样机械运动的轨道。在聚合酶模式下，它在每一步中通过一个核苷酸延伸新生 DNA。然而，每当它因错误掺入不正确的核苷酸而犯错误时，它可以切换到外切核酸酶模式。在后一种模式下，它在切换回聚合酶模式之前切除错误的核苷酸。我们开发了一个 DNA 复制的随机动力学模型，模拟了一个体外实验，其中单链 DNA 在机械张力 F 的作用下，通过单个 DNAP 转化为双链 DNA。复制的平均速率的 F 依赖性，这取决于 DNAP 的聚合酶和外切核酸酶活性的速率，与相应的实验结果具有很好的定性一致性。我们引入了九个新的独特条件停留时间的 DNAP。使用首次通过时间的方法，我们还为这些条件停留时间的概率分布导出了精确的解析表达式。这些分布的 F 依赖性原则上可以通过单分子实验获得。
