Supercoiling and looping promote DNA base accessibility and coordination among distant sites.
Supercoiling and looping promote DNA base accessibility and coordination among distant sites.
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DOI：
10.1038/s41467-021-25936-2
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发表时间：
2021-09-28
影响因子：
16.6
通讯作者：
Zechiedrich L
中科院分区：
文献类型：
--
作者：
Fogg JM;Judge AK;Stricker E;Chan HL;Zechiedrich L
细胞中的DNA是超螺旋的，并被限制成环，这种超螺旋和成环影响DNA活性的各个方面。我们在这里表明，负超螺旋传递机械应力沿着DNA骨架破坏碱基配对在特定的遥远的网站。远距离位点之间的协同作用使某些序列定位于超螺旋顶端。碱基对的破坏使超螺旋顶端发生急剧弯曲，这有助于DNA扭转以减轻扭转应变。这些过程的耦合可能有助于防止与基因组不稳定性相关的广泛变性。我们的研究结果为DNA如何形成短环提供了一个模型，这是许多基本过程所必需的，以及细胞如何使用DNA环来定位缺口以促进修复。此外，我们的研究结果揭示了碱基配对的位点特异性破坏与DNA的3-D构象之间的复杂相互作用，这影响了基因组如何储存，复制，转录，修复以及DNA活性的许多其他方面。DNA超螺旋可以导致DNA双螺旋的负超螺旋的欠卷绕或正超螺旋的过卷绕。在这里，作者揭示了DNA超螺旋诱导的序列依赖性碱基配对，DNA环和DNA分子形状之间的动态关系。
DNA in cells is supercoiled and constrained into loops and this supercoiling and looping influence every aspect of DNA activity. We show here that negative supercoiling transmits mechanical stress along the DNA backbone to disrupt base pairing at specific distant sites. Cooperativity among distant sites localizes certain sequences to superhelical apices. Base pair disruption allows sharp bending at superhelical apices, which facilitates DNA writhing to relieve torsional strain. The coupling of these processes may help prevent extensive denaturation associated with genomic instability. Our results provide a model for how DNA can form short loops, which are required for many essential processes, and how cells may use DNA loops to position nicks to facilitate repair. Furthermore, our results reveal a complex interplay between site-specific disruptions to base pairing and the 3-D conformation of DNA, which influences how genomes are stored, replicated, transcribed, repaired, and many other aspects of DNA activity. DNA supercoiling can result in underwinding with negative supercoiling or overwinding with positive supercoiling of the DNA double helix. Here the authors reveal insights into the dynamic relationship between DNA supercoiling-induced sequence-dependent disruptions to base pairing, DNA looping, and the shape of the DNA molecule.
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影响因子：
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作者：
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作者：
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