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Beyond DnaA: The role of DNA topology and DNA methylation in bacterial replication initiation

机译:超越DnaA:DNA拓扑结构和DNA甲基化在细菌复制起始中的作用

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The replication of chromosomal DNA is a fundamental event in the life cycle of every cell. The first step of replication, initiation, is controlled by multiple factors to ensure only one round of replication per cell cycle. The process of initiation has been described most thoroughly for bacteria, especially Escherichia coli, and involves many regulatory proteins that vary considerably between different species. These proteins control the activity of the two key players of initiation in bacteria: the initiator protein DnaA and the origin of chromosome replication (oriC). Factors involved in the control of the availability, activity, or oligomerization of DnaA during initiation are generally regarded as the most important and thus have been thoroughly characterized. Other aspects of the initiation process, such as origin accessibility and susceptibility to unwinding, have been less explored. However, recent findings indicate that these factors have a significant role. This review focuses on DNA topology, conformation, and methylation as important factors that regulate the initiation process in bacteria. We present a comprehensive summary of the factors involved in the modulation of DNA topology, both locally at oriC and more globally at the level of the entire chromosome. We show clearly that the conformation of oriC dynamically changes, and control of this conformation constitutes another, important factor in the regulation of bacterial replication initiation. Furthermore, the process of initiation appears to be associated with the dynamics of the entire chromosome and this association is an important but largely unexplored phenomenon.
机译:染色体DNA的复制是每个细胞生命周期中的一个基本事件。复制的第一步即启动受多个因素控制,以确保每个细胞周期仅进行一轮复制。对于细菌,尤其是大肠杆菌,已经最全面地描述了启动过程,并且涉及许多调节蛋白,这些调节蛋白在不同物种之间差异很大。这些蛋白控制着细菌中两个关键的启动子活性:启动子蛋白DnaA和染色体复制起点(oriC)。在启动过程中,与DnaA的可用性,活性或低聚控制有关的因素通常被认为是最重要的,因此已得到充分表征。起始过程的其他方面,例如原产地可到达性和放卷的敏感性,已被较少地研究。但是,最近的发现表明这些因素具有重要作用。这篇综述着重于DNA拓扑,构象和甲基化,它们是调节细菌起始过程的重要因素。我们提供了涉及DNA拓扑结构调节的因素的全面总结,无论是在oriC本地还是在整个染色体水平上更全局。我们清楚地表明oriC的构象动态变化,并且对该构象的控制构成了细菌复制起始调控中的另一个重要因素。此外,起始过程似乎与整个染色体的动力学有关,这种关联是一个重要的现象,但很大程度上是未探索的现象。

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