近日，國(guó)際著名雜志Molecular Microbiology上刊登了紐約州立大學(xué)研究者的最新研究成果“Evidence for roles of the Escherichia coli Hda protein beyond regulatory inactivation of DnaA”,，文章中,，研究者揭示了大腸桿菌Hda蛋白在維持細(xì)胞生存上的重要功能及證據(jù)。
大腸桿菌,，又名腸埃希氏菌(E. coli),，某些大腸桿菌菌群對(duì)人和動(dòng)物有致病性，尤其對(duì)嬰兒和幼畜,，常引起嚴(yán)重腹瀉和敗血癥,。大腸桿菌中ATP緊密形式的DnaA蛋白可以在復(fù)制起點(diǎn)Oric位置或者某些基因的操縱子部位結(jié)合其DnaA盒子（DnaA Boxes），最終開始其復(fù)制轉(zhuǎn)錄起始,。
Hda蛋白和其β滑行夾子一起可以通過(guò)鈍化DnaA（DnaA的調(diào)解失活,，RIDA）來(lái)激活其ATP酶活性，最終在DNA復(fù)制水平來(lái)調(diào)節(jié)DnaA的活性,。
在文章中,，研究者使用了大腸桿菌dnaN159的突變體，其可以表達(dá)β159“夾子蛋白質(zhì)”來(lái)獲得Hada蛋白協(xié)調(diào)復(fù)制的活性行為,。Had的高表達(dá)可以在兩種水平（Pol II和Pol IV）來(lái)阻礙大腸桿菌dnaN159的突變體的生長(zhǎng),，這就表明Hda可以作為管理者來(lái)管理Pols的活動(dòng)的角色。Hda的高水平表達(dá)也和食品添加劑-硝基糠棕的敏感性直接相關(guān),。
使用大腸桿菌dnaN159的突變體,，研究者發(fā)現(xiàn)了24個(gè)新的hda的等位基因，其中有四個(gè)可以在RIDA缺失的情況下支持大腸桿菌的活力,。因此研究者的研究揭示了Hda對(duì)于細(xì)胞生存維持的功能角色,，DnaA的調(diào)節(jié)失活也許并不是必須的。（生物谷Bioon.com）
doi:10.1111/j.1365-2958.2012.08129.x
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Evidence for roles of the Escherichia coli Hda protein beyond regulatory inactivation of DnaA
Jamie C. Baxter1,2, Mark D. Sutton1,2,*
The ATP-bound form of the Escherichia coli DnaA protein binds ‘DnaA boxes’ present in the origin of replication (oriC) and operator sites of several genes, including dnaA, to co-ordinate their transcription with initiation of replication. The Hda protein, together with the β sliding clamp, stimulates the ATPase activity of DnaA via a process termed regulatory inactivation of DnaA (RIDA), to regulate the activity of DnaA in DNA replication. Here, we used the mutant dnaN159 strain, which expresses the β159 clamp protein, to gain insight into how the actions of Hda are co-ordinated with replication. Elevated expression of Hda impeded growth of the dnaN159 strain in a Pol II- and Pol IV-dependent manner, suggesting a role for Hda managing the actions of these Pols. In a wild-type strain, elevated levels of Hda conferred sensitivity to nitrofurazone, and suppressed the frequency of −1 frameshift mutations characteristic of Pol IV, while loss of hda conferred cold sensitivity. Using the dnaN159 strain, we identified 24 novel hda alleles, four of which supported E. coli viability despite their RIDA defect. Taken together, these findings suggest that although one or more Hda functions are essential for cell viability, RIDA may be dispensable.
