Fifty years of DNA "breathing": Reflections on old and new approaches.
Fifty years of DNA "breathing": Reflections on old and new approaches.
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DOI：
10.1002/bip.22347
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发表时间：
2013-12
期刊：
影响因子：
2.9
通讯作者：
Marcus, Andrew H.
中科院分区：
文献类型：
--
作者：
von Hippel, Peter H.;Johnson, Neil P.;Marcus, Andrew H.
关键词：
基因的编码序列以及许多其他涉及基因组表达的调控信息位于DNA双链的“内部”。因此，从DNA碱基序列读取这些信息的“大分子机器”必须以某种方式进入DNA的“内部”。双链（ds）DNA在生理温度下是一个高度结构化且协同稳定的系统，但也只是勉强稳定，在略高于生理温度时会发生协同的“熔解相变”。此外，由于其长度和序列的不均一性，富含AT的片段比富含GC的片段稳定性差，DNA基因组以多态方式“熔解”。因此，DNA基因组在生理温度下也必然会表现出热驱动的结构（“呼吸”）波动，这应该反映了在熔解温度附近双链DNA稳定性的不均一性。因此，双链DNA的许多呼吸波动可能也依赖于序列，并且很可能包含在涉及双链DNA“打开”的位点特异性结合反应中可被调控蛋白和蛋白复合物“读取”和利用的信息。我们的实验室大约50年来一直致力于研究双链DNA的呼吸波动。在这篇“回顾”文章中，我们对这些研究进行了一个相对按时间顺序的综述，从使用简单的化学探针（如氢交换、甲醛和简单的DNA“熔解”蛋白）来检测双链DNA结构的局部稳定性开始，最终发展到可以用于实时监测调控复合物与其双链DNA靶标之间依赖呼吸的相互作用的复杂光谱方法。
The coding sequences for genes, and much other regulatory information involved in genome expression, are located ‘inside’ the DNA duplex. Thus the ‘macromolecular machines’ that read-out this information from the base sequence of the DNA must somehow access the DNA ‘interior’. Double-stranded (ds) DNA is a highly structured and cooperatively stabilized system at physiological temperatures, but is also only marginally stable and undergoes a cooperative ‘melting phase transition’ at temperatures not far above physiological. Furthermore, due to its length and heterogeneous sequence, with AT-rich segments being less stable than GC-rich segments, the DNA genome ‘melts’ in a multistate fashion. Therefore the DNA genome must also manifest thermally driven structural (‘breathing’) fluctuations at physiological temperatures that should reflect the heterogeneity of the dsDNA stability near the melting temperature. Thus many of the breathing fluctuations of dsDNA are likely also to be sequence dependent, and could well contain information that should be ‘readable’ and useable by regulatory proteins and protein complexes in site-specific binding reactions involving dsDNA ‘opening’. Our laboratory has been involved in studying the breathing fluctuations of duplex DNA for about 50 years. In this ‘Reflections’ article we present a relatively chronological overview of these studies, starting with the use of simple chemical probes (such as hydrogen exchange, formaldehyde and simple DNA ‘melting’ proteins) to examine the local stability of the dsDNA structure, and culminating in sophisticated spectroscopic approaches that can be used to monitor the breathing-dependent interactions of regulatory complexes with their duplex DNA targets in ‘real time’.
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影响因子：
14.9
作者：
Datta, Kausiki;Johnson, Neil P.;von Hippel, Peter H.
通讯作者：
von Hippel, Peter H.
影响因子：
4.8
作者：
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通讯作者：
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影响因子：
5.6
作者：
Datta, Kausiki;Johnson, Neil P.;von Hippel, Peter H.
通讯作者：
von Hippel, Peter H.
影响因子：
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作者：
Johnson, NP;Baase, WA;von Hippel, PH
通讯作者：
von Hippel, PH
DOI：
10.1073/pnas.1210040109
发表时间：
2012-08-21
影响因子：
11.1
作者：
Jose, Davis;Weitzel, Steven E.;von Hippel, Peter H.
通讯作者：
von Hippel, Peter H.