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DNA分支迁移的离散和连续数学模型。

Discrete and continuous mathematical models of DNA branch migration.

作者信息

Bruist Michael F, Myers Eric

机构信息

Department of Chemistry & Biochemistry, University of the Sciences in Philadelphia, Philadelphia, PA 19104-4495, U.S.A.

出版信息

J Theor Biol. 2003 Jan 21;220(2):139-56. doi: 10.1006/jtbi.2003.3121.

Abstract

DNA junctions, known as Holliday junctions, are intermediates in genetic recombination between DNAs. In this structure, two double-stranded DNA helices with similar sequence are joined at a branch point. The branch point can move along these helices when strands with the same sequence are exchanged. Such branch migration is modeled as a random walk. First, we model this process discretely, such that the motion of the branch is represented as transfer between discrete compartments. This is useful in analysing the results of DNA branch migration on junction comprised of synthetic oligonucleotides. The limit in which larger numbers of smaller steps go to continuous motion of the branch is also considered. We show that the behavior of the continuous system is very similar to that of the discrete system when there are more than just a few compartments. Thus, even branch migration on oligonucleotides can be viewed as a continuous process. One consequence of this is that a step size must be assumed when determining rate constants of branch migration. We compare migration where forward and backward movements of the branch are equally probable to biased migration where one direction is favored over the other. In the latter case larger differences between the discrete and continuous cases are predicted, but the differences are still small relative to the experimental error associated with experiments to measure branch migration in oligonucleotides.

摘要

DNA连接体,即霍利迪连接体,是DNA之间基因重组的中间体。在这种结构中,两条具有相似序列的双链DNA螺旋在一个分支点处相连。当具有相同序列的链发生交换时,分支点可以沿着这些螺旋移动。这种分支迁移被建模为随机游走。首先,我们对这个过程进行离散建模,使得分支的运动表示为离散隔室之间的转移。这对于分析由合成寡核苷酸组成的连接体上的DNA分支迁移结果很有用。还考虑了大量较小步长趋近于分支连续运动的极限情况。我们表明,当隔室数量不止几个时,连续系统的行为与离散系统非常相似。因此,即使是寡核苷酸上的分支迁移也可以被视为一个连续过程。这样做的一个结果是,在确定分支迁移速率常数时必须假设一个步长。我们比较了分支向前和向后移动概率相等的迁移与一个方向比另一个方向更受青睐的有偏迁移。在后一种情况下,预测离散和连续情况之间的差异会更大,但相对于测量寡核苷酸中分支迁移的实验所涉及的实验误差而言,这些差异仍然很小。

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