Pathways of DNA unlinking: A story of stepwise simplification.

Pathways of DNA unlinking: A story of stepwise simplification.
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DOI:
10.1038/s41598-017-12172-2
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发表时间:
2017-09-29
期刊:
影响因子:
4.6
通讯作者:
Vazquez M
Vazquez M
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Stolz R;Yoshida M;Brasher R;Flanner M;Ishihara K;Sherratt DJ;Shimokawa K;Vazquez M

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在大肠杆菌中,DNA 复制产生相互连接的染色体。控制与复制相关的拓扑变化并将新复制的染色体恢复到未连接的单体状态对于细胞生存至关重要。在拓扑异构酶 topoIV 缺失的情况下,位点特异性重组复合物 XerCD-dif-FtsK 可以通过局部重连来消除复制链路。我们之前在数学上证明了存在一种独特的最小路径,可以通过重新连接来断开复制链接,同时逐步降低拓扑复杂性。然而,重新连接保留或增加拓扑复杂性的可能性在生物学上是合理的。那么,在这种情况下,是否还有其他的解除链接的途径呢?哪个最有可能?我们在最小解链路径的分析和数值研究中考虑这些问题。我们使用马尔可夫链蒙特卡罗算法和多个马尔可夫链采样来对 491 个不同的基底拓扑、166 个结和 325 个链路上的局部重连接进行建模,并区分连接总共 881 个不同拓扑的路径。我们的结论是,在更严格的假设下发现的解除复制链接的最小路径是最有可能的。我们还提供了断开 6 交叉复制链接的确切结果。这些结果指出了通过局部重新连接进行拓扑简化的一般过程,其应用超出了 DNA 范围。
In Escherichia coli DNA replication yields interlinked chromosomes. Controlling topological changes associated with replication and returning the newly replicated chromosomes to an unlinked monomeric state is essential to cell survival. In the absence of the topoisomerase topoIV, the site-specific recombination complex XerCD- dif-FtsK can remove replication links by local reconnection. We previously showed mathematically that there is a unique minimal pathway of unlinking replication links by reconnection while stepwise reducing the topological complexity. However, the possibility that reconnection preserves or increases topological complexity is biologically plausible. In this case, are there other unlinking pathways? Which is the most probable? We consider these questions in an analytical and numerical study of minimal unlinking pathways. We use a Markov Chain Monte Carlo algorithm with Multiple Markov Chain sampling to model local reconnection on 491 different substrate topologies, 166 knots and 325 links, and distinguish between pathways connecting a total of 881 different topologies. We conclude that the minimal pathway of unlinking replication links that was found under more stringent assumptions is the most probable. We also present exact results on unlinking a 6-crossing replication link. These results point to a general process of topology simplification by local reconnection, with applications going beyond DNA.
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