The orisome: structure and function.
The orisome: structure and function.
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DOI：
10.3389/fmicb.2015.00545
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发表时间：
2015
影响因子：
5.2
通讯作者：
Grimwade JE
中科院分区：
文献类型：
--
作者：
Leonard AC;Grimwade JE
在所有细菌的细胞分裂周期中，称为orisomes的DNA-蛋白质复合物触发染色体复制的开始。Orisome组装是分阶段的，并且受到严格的调节，以确保DNA合成在精确的时间开始，并且每个周期在每个起点仅一次。Orisomes包含多个拷贝的起始蛋白DnaA，该蛋白在与独特染色体复制起点oriC中特定定位的识别位点相互作用后发生寡聚体。由于DnaA是高度保守的，因此合乎逻辑的是，预期所有细菌orisomes将共享基本属性。事实上，尽管机制细节仍有待确定，但所有细菌的orisomes都能够解旋oriC DNA，并有助于将DNA解旋酶装载到单链上。然而，对oriCs的比较分析表明，DnaA识别位点的排列和数量在细菌类型之间是令人惊讶的可变的，这表明有许多途径来产生功能性orisome复合物。存在的基本问题是，为什么存在这些不同的路径，以及不同类型的细菌必须共享orisomes的哪些特征。在这篇综述中，我们提出了目前的理解orisome组装和功能在大肠杆菌和比较的γ-变形菌的相关成员之间的复制起点。从这些信息中，我们提出，orisome组装的多样性反映了需要调节起源DNA的构象，以及提供一个适当的细胞周期定时机制，反映了细菌的生活方式。我们认为，识别orisome组装中的共享步骤可能会揭示新抗生素的特别好的靶点。
During the cell division cycle of all bacteria, DNA-protein complexes termed orisomes trigger the onset of chromosome duplication. Orisome assembly is both staged and stringently regulated to ensure that DNA synthesis begins at a precise time and only once at each origin per cycle. Orisomes comprise multiple copies of the initiator protein DnaA, which oligomerizes after interacting with specifically positioned recognition sites in the unique chromosomal replication origin, oriC. Since DnaA is highly conserved, it is logical to expect that all bacterial orisomes will share fundamental attributes. Indeed, although mechanistic details remain to be determined, all bacterial orisomes are capable of unwinding oriC DNA and assisting with loading of DNA helicase onto the single-strands. However, comparative analysis of oriCs reveals that the arrangement and number of DnaA recognition sites is surprisingly variable among bacterial types, suggesting there are many paths to produce functional orisome complexes. Fundamental questions exist about why these different paths exist and which features of orisomes must be shared among diverse bacterial types. In this review we present the current understanding of orisome assembly and function in Escherichia coli and compare the replication origins among the related members of the Gammaproteobacteria. From this information we propose that the diversity in orisome assembly reflects both the requirement to regulate the conformation of origin DNA as well as to provide an appropriate cell cycle timing mechanism that reflects the lifestyle of the bacteria. We suggest that identification of shared steps in orisome assembly may reveal particularly good targets for new antibiotics.