DNA Looping Provides for "Intersegmental Hopping" by Proteins: A Mechanism for Long-Range Site Localization
DNA Looping Provides for "Intersegmental Hopping" by Proteins: A Mechanism for Long-Range Site Localization
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DOI：
10.1016/j.jmb.2014.08.002
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发表时间：
2014-10-23
影响因子：
5.6
通讯作者：
Reich, Norbert O.
中科院分区：
文献类型：
--
作者：
Pollak, Adam J.;Chin, Aaron T.;Reich, Norbert O.
关于转录因子和DNA修饰酶如何被动地定位DNA上的特定位点的研究还没有与一组足够的机制相协调，这些机制可以充分解释这一过程的效率和速度。当考虑到这些DNA结合/修饰蛋白具有不同水平的细胞拷贝数和基因组识别位点密度时，这尤其正确。单体细菌DNA腺嘌呤甲基转移酶（Dam）负责整个染色体的快速甲基化（每个细胞只有大约100个Dam拷贝）和控制几种人类病原体中毒力基因表达的紧密间隔位点的调节甲基化。具有挑衅性的是，我们发现，大坝之间的旅行最有效的识别位点时，这些网站是类似的500 bp分开。我们认为，这是表现为大坝之间移动的远端区域在同一个DNA分子，这是介导的DNA循环，一种现象，我们指定为段间跳跃。重要的是，在其他系统中发现的中间体，包括两个同时结合的环状DNA链，在这里不涉及。我们的研究结果表明，intersegmental hopping有助于酶的持续合成能力（多个修改），这调用最近的报告表明，DNA循环可以帮助网站的发现。考虑到某些生物学背景，片段间跳跃可能被其他序列特异性DNA结合蛋白，如转录因子和调节蛋白使用。虽然许多研究小组提出了这种机制的一般形式，但我们在进行性催化的背景下对DNA循环的考虑提供了新的机制见解和区别。爱思唯尔有限公司出版
Studies on how transcription factors and DNA modifying enzymes passively locate specific sites on DNA have yet to be reconciled with a sufficient set of mechanisms that can adequately account for the efficiency and speed of this process. This is especially true when considering that these DNA binding/modifying proteins have diverse levels of both cellular copy numbers and genomic recognition site densities. The monomeric bacterial DNA adenine methyltransferase (Dam) is responsible for the rapid methylation of the entire chromosome (with only similar to 100 Dam copies per cell) and the regulated methylation of closely spaced sites that controls the expression of virulence genes in several human pathogens. Provocatively, we find that Dam travels between its recognition sites most efficiently when those sites are similar to 500 bp apart. We propose that this is manifested by Dam moving between distal regions on the same DNA molecule, which is mediated by DNA looping, a phenomenon we designate as intersegmental hopping. Importantly, an intermediate found in other systems including two simultaneously bound, looped DNA strands is not involved here. Our results suggest that intersegmental hopping contributes to enzymatic processivity (multiple modifications), which invoke recent reports demonstrating that DNA looping can assist in site finding. Intersegmental hopping is possibly used by other sequence-specific DNA binding proteins, such as transcription factors and regulatory proteins, given certain biological context. While a general form of this mechanism is proposed by many research groups, our consideration of DNA looping in the context of processive catalysis provides new mechanistic insights and distinctions. Published by Elsevier Ltd.