日,，來自UC Santa Barbara的研究人員在細(xì)菌中發(fā)現(xiàn)了一種酶,，其隨著DNA向前移動(dòng)時(shí)酶的能力發(fā)生改變可以修飾細(xì)菌自身的遺傳物質(zhì)，這項(xiàng)發(fā)現(xiàn)為以后生物醫(yī)藥和其它科學(xué)應(yīng)用提供了新的思路,，相關(guān)研究成果刊登在了國(guó)際雜志Journal of Biological Chemistry上,。
大腸桿菌的適應(yīng)機(jī)制可以允許其改變自己的表型，比如細(xì)菌如果需要食物,，它就會(huì)粘附在宿主組織上并且進(jìn)行繁殖,，這時(shí)候大腸桿菌便可以形成菌毛等結(jié)構(gòu)，這就允許細(xì)菌移動(dòng),，粘附已形成更多的遺傳物質(zhì),。
菌毛的形成受某種遺傳學(xué)機(jī)制的控制，同時(shí)也是一種DNA酶-DNA腺嘌呤甲基轉(zhuǎn)移酶（Dam）的標(biāo)志物,。比較流行的觀點(diǎn)認(rèn)為Dam沿著細(xì)菌雙螺旋DNA的某個(gè)位點(diǎn)滑動(dòng)從而尋找GATC位點(diǎn),。實(shí)際上Dam可以沿著DNA上一個(gè)或者多個(gè)位點(diǎn)進(jìn)行滑動(dòng)。使用不同長(zhǎng)度以及甲基化位點(diǎn)不同的多股遺傳工程化的DNA進(jìn)行研究,，研究者發(fā)現(xiàn)了Dam的會(huì)經(jīng)常“跳躍工作”,，并且依賴于位點(diǎn)的聚集。聚集的GATC位點(diǎn)常常和基因表達(dá)相關(guān),，文章中,，研究者發(fā)現(xiàn)，未定位在GATC序列上的時(shí)間越長(zhǎng),，酶所經(jīng)歷的跳躍變化越少,，但是一旦引入GATC序列，就會(huì)激發(fā)這種機(jī)制的發(fā)生,。
文章中,，研究者表示，跳躍現(xiàn)象（hopping）可以解釋為什么DNA修飾酶發(fā)現(xiàn)其結(jié)合位點(diǎn)的效率,，盡管存在數(shù)量驚人的非特異性DNA,，但是跳躍現(xiàn)象使得DNA酶可以輕松識(shí)別其結(jié)合位點(diǎn)，而且這些酶可以修飾不僅僅是一個(gè)位點(diǎn),。
研究者分析了大腸桿菌的行為,、毒力因子以及其增殖的能力，并且研究者表示,，學(xué)習(xí)如何開啟大腸桿菌的毒力能力對(duì)于我們應(yīng)對(duì)細(xì)菌感染非常重要,。研究者Pollak表示，如果我們可以阻止其開關(guān),，那么就可以避免不必要的感染,。（生物谷Bioon.com）
編譯自：Discovery of 'Hopping' of Bacterial Enzyme Gives Insight Into Gene Expression
doi:10.1074/jbc.M111.332502
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PMID:
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.
