日，来自UC Santa Barbara的研究人员在细菌中发现了一种酶，其随着DNA向前移动时酶的能力发生改变可以修饰细菌自身的遗传物质，这项发现为以后生物医药和其它科学应用提供了新的思路，相关研究成果刊登在了国际杂志Journal of Biological Chemistry上。
大肠杆菌的适应机制可以允许其改变自己的表型，比如细菌如果需要食物，它就会粘附在宿主组织上并且进行繁殖，这时候大肠杆菌便可以形成菌毛等结构，这就允许细菌移动，粘附已形成更多的遗传物质。
菌毛的形成受某种遗传学机制的控制，同时也是一种DNA酶-DNA腺嘌呤甲基转移酶（Dam）的标志物。比较流行的观点认为Dam沿着细菌双螺旋DNA的某个位点滑动从而寻找GATC位点。实际上Dam可以沿着DNA上一个或者多个位点进行滑动。使用不同长度以及甲基化位点不同的多股遗传工程化的DNA进行研究，研究者发现了Dam的会经常“跳跃工作”，并且依赖于位点的聚集。聚集的GATC位点常常和基因表达相关，文章中，研究者发现，未定位在GATC序列上的时间越长，酶所经历的跳跃变化越少，但是一旦引入GATC序列，就会激发这种机制的发生。
文章中，研究者表示，跳跃现象（hopping）可以解释为什么DNA修饰酶发现其结合位点的效率，尽管存在数量惊人的非特异性DNA，但是跳跃现象使得DNA酶可以轻松识别其结合位点，而且这些酶可以修饰不仅仅是一个位点。
研究者分析了大肠杆菌的行为、毒力因子以及其增殖的能力，并且研究者表示，学习如何开启大肠杆菌的毒力能力对于我们应对细菌感染非常重要。研究者Pollak表示，如果我们可以阻止其开关，那么就可以避免不必要的感染。（生物谷Bioon.com）
编译自：Discovery of 'Hopping' of Bacterial Enzyme Gives Insight Into Gene Expression
doi:10.1074/jbc.M111.332502
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Proximal Recognition Sites Facilitate Intrasite Hopping by DNA Adenine Methyltransferase MECHANISTIC EXPLORATION OF EPIGENETIC GENE REGULATION
Adam J. Pollak and Norbert O. Reich1
The methylation of adenine in palindromic 5′-GATC-3′ sites by Escherichia coli Dam supports diverse roles, including the essential regulation of virulence genes in several human pathogens. As a result of a unique hopping mechanism, Dam methylates both strands of the same site prior to fully dissociating from the DNA, a process referred to as intrasite processivity. The application of a DpnI restriction endonuclease-based assay allowed the direct interrogation of this mechanism with a variety of DNA substrates. Intrasite processivity is disrupted when the DNA flanking a single GATC site is longer than 400 bp on either side. Interestingly, the introduction of a second GATC site within this flanking DNA reinstates intrasite methylation of both sites. Our results show that intrasite methylation occurs only when GATC sites are clustered, as is found in gene segments both known and postulated to undergo in vivo epigenetic regulation by Dam methylation. We propose a model for intrasite methylation in which Dam bound to flanking DNA is an obligate intermediate. Our results provide insights into how intrasite processivity, which appears to be context-dependent, may contribute to the diverse biological roles that are carried out by Dam.
