Racko Dusan, Benedetti Fabrizio, Dorier Julien, Burnier Yannis, Stasiak Andrzej
Center for Integrative Genomics, University of Lausanne, 1015-Lausanne, Switzerland SIB Swiss Institute of Bioinformatics, 1015-Lausanne, Switzerland Polymer Institute of the Slovak Academy of Sciences, 842 36 Bratislava, Slovakia.
Center for Integrative Genomics, University of Lausanne, 1015-Lausanne, Switzerland SIB Swiss Institute of Bioinformatics, 1015-Lausanne, Switzerland.
Nucleic Acids Res. 2015 Sep 3;43(15):7229-36. doi: 10.1093/nar/gkv683. Epub 2015 Jul 6.
Due to the helical structure of DNA the process of DNA replication is topologically complex. Freshly replicated DNA molecules are catenated with each other and are frequently knotted. For proper functioning of DNA it is necessary to remove all of these entanglements. This is done by DNA topoisomerases that pass DNA segments through each other. However, it has been a riddle how DNA topoisomerases select the sites of their action. In highly crowded DNA in living cells random passages between contacting segments would only increase the extent of entanglement. Using molecular dynamics simulations we observed that in actively supercoiled DNA molecules the entanglements resulting from DNA knotting or catenation spontaneously approach sites of nicks and gaps in the DNA. Type I topoisomerases, that preferentially act at sites of nick and gaps, are thus naturally provided with DNA-DNA juxtapositions where a passage results in an error-free DNA unknotting or DNA decatenation.
由于DNA的螺旋结构，DNA复制过程在拓扑学上很复杂。新复制的DNA分子相互连环，还经常打结。为使DNA正常发挥功能，有必要消除所有这些缠结。这是由DNA拓扑异构酶完成的，它们使DNA片段相互穿过。然而，DNA拓扑异构酶如何选择其作用位点一直是个谜。在活细胞中高度拥挤的DNA环境下，接触片段之间的随机穿过只会增加缠结程度。通过分子动力学模拟，我们观察到在活跃超螺旋的DNA分子中，由DNA打结或连环产生的缠结会自发靠近DNA中的切口和缺口位点。因此，优先作用于切口和缺口位点的I型拓扑异构酶自然会遇到DNA-DNA并列情况，在此处进行一次穿过就能实现无差错的DNA解结或DNA解连环。
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