论文标题

DNA不匹配修复中分离搜索机制的潜在进化优势

Potential evolutionary advantage of a dissociative search mechanism in DNA mismatch repair

论文作者

Crocker, Kyle, London, James, Medina, Andrés, Fishel, Richard, Bundschuh, Ralf

论文摘要

参与DNA不匹配修复的蛋白质复合物似乎沿DSDNA扩散,以通过分离机制定位半甲基化切口部位。在这里,我们研究了这些复合物通过半分析的蒙特卡洛计算来定位给定目标位点的概率,该计算跟踪复合物的关联和解离。我们将这种概率与使用非分离性扩散扫描获得的概率进行了比较,并确定在实验观察到的扩散常数,搜索距离和搜索持续时间$ \ textit {in Better {Intter} $中既没有重要的优势,也没有缺点,也不具有与搜索的高度相关的搜索范围,并且在高度搜索机构方面都有足够的范围,并且是高度均可供应。此外,我们研究了物理上现实的扩散常数,半甲基化位点距离和关联寿命的空间,并确定与非分解性搜索相比,分离式搜索效率或多或少有效的区域。我们得出的结论是,在大多数物理现实的参数空间中,分离搜索机制是有利的。

Protein complexes involved in DNA mismatch repair appear to diffuse along dsDNA in order to locate a hemimethylated incision site via a dissociative mechanism. Here, we study the probability that these complexes locate a given target site via a semi-analytic, Monte Carlo calculation that tracks the association and dissociation of the complexes. We compare such probabilities to those obtained using a non-dissociative diffusive scan, and determine that for experimentally observed diffusion constants, search distances, and search durations $\textit{in vitro}$, there is neither a significant advantage nor disadvantage associated with the dissociative mechanism in terms of probability of successful search, and that both search mechanisms are highly efficient for a majority of hemimethylated site distances. Furthermore, we examine the space of physically realistic diffusion constants, hemimethylated site distances, and association lifetimes and determine the regions in which dissociative searching is more or less efficient than non-dissociative searching. We conclude that the dissociative search mechanism is advantageous in the majority of the physically realistic parameter space.

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