Sharma Ajeet K, Chowdhury Debashish
Department of Physics, Indian Institute of Technology, Kanpur 208016, India.
Phys Rev E Stat Nonlin Soft Matter Phys. 2012 Jul;86(1 Pt 1):011913. doi: 10.1103/PhysRevE.86.011913. Epub 2012 Jul 16.
DNA polymerase (DNAP) is a dual-purpose enzyme that plays two opposite roles in two different situations during DNA replication. It plays its a normal role as a polymerase catalyzing the elongation of a new DNA molecule by adding a monomer. However, it can switch to the role of an exonuclease and shorten the same DNA by cleavage of the last incorporated monomer from the nascent DNA. Just as misincorporated nucleotides can escape exonuclease causing a replication error, the correct nucleotide may get sacrificed unnecessarily by erroneous cleavage. The interplay of polymerase and exonuclease activities of a DNAP is explored here by developing a minimal stochastic kinetic model of DNA replication. Exact analytical expressions are derived for a few key statistical distributions; these characterize the temporal patterns in the mechanical stepping and the chemical (cleavage) reaction. The Michaelis-Menten-like analytical expression derived for the average rates of these two processes not only demonstrate the effects of their coupling, but are also utilized to measure the extent of replication error and erroneous cleavage.
DNA聚合酶（DNAP）是一种具有双重功能的酶，在DNA复制过程中的两种不同情况下发挥着两种相反的作用。它作为聚合酶发挥正常作用，通过添加单体来催化新DNA分子的延伸。然而，它可以转变为核酸外切酶的角色，通过从新生DNA上切割最后掺入的单体来缩短相同的DNA。正如错误掺入的核苷酸可以逃脱核酸外切酶的作用而导致复制错误一样，正确的核苷酸可能会因错误切割而被不必要地牺牲。本文通过建立一个最小的DNA复制随机动力学模型，探讨了DNAP的聚合酶和核酸外切酶活性之间的相互作用。推导了一些关键统计分布的精确解析表达式；这些表达式表征了机械步进和化学（切割）反应中的时间模式。为这两个过程的平均速率推导的类似米氏方程的解析表达式不仅证明了它们耦合的影响，还用于测量复制错误和错误切割的程度。
