Section for Functional Genomics and Center for Bacterial Stress Response and Persistence, Department of Biology, University of Copenhagen Copenhagen, Denmark.
Front Mol Biosci. 2016 Jun 28;3:29. doi: 10.3389/fmolb.2016.00029. eCollection 2016.
Chromosome replication in Escherichia coli is initiated from a single origin, oriC. Initiation involves a number of DNA binding proteins, but only DnaA is essential and specific for the initiation process. DnaA is an AAA+ protein that binds both ATP and ADP with similar high affinities. DnaA associated with either ATP or ADP binds to a set of strong DnaA binding sites in oriC, whereas only DnaA(ATP) is capable of binding additional and weaker sites to promote initiation. Additional DNA binding proteins act to ensure that initiation occurs timely by affecting either the cellular mass at which DNA replication is initiated, or the time window in which all origins present in a single cell are initiated, i.e. initiation synchrony, or both. Overall, these DNA binding proteins modulate the initiation frequency from oriC by: (i) binding directly to oriC to affect DnaA binding, (ii) altering the DNA topology in or around oriC, (iii) altering the nucleotide bound status of DnaA by interacting with non-coding chromosomal sequences, distant from oriC, that are important for DnaA activity. Thus, although DnaA is the key protein for initiation of replication, other DNA-binding proteins act not only on oriC for modulation of its activity but also at additional regulatory sites to control the nucleotide bound status of DnaA. Here we review the contribution of key DNA binding proteins to the tight regulation of chromosome replication in E. coli cells.
大肠杆菌中的染色体复制从单个原点 oriC 开始。起始涉及许多 DNA 结合蛋白，但只有 DnaA 是起始过程所必需和特异的。DnaA 是一种 AAA+ 蛋白，与 ATP 和 ADP 都具有相似的高亲和力结合。与 ATP 或 ADP 结合的 DnaA 与 oriC 中的一组强 DnaA 结合位点结合，而只有 DnaA(ATP)能够结合额外的较弱位点以促进起始。其他 DNA 结合蛋白通过影响 DNA 复制起始的细胞质量或单个细胞中所有原点起始的时间窗口（即起始同步性）或两者来确保起始的时机。总的来说，这些 DNA 结合蛋白通过以下方式调节 oriC 的起始频率：（i）直接与 oriC 结合以影响 DnaA 结合，（ii）改变 oriC 内或周围的 DNA 拓扑结构，（iii）通过与对 DnaA 活性很重要的远离 oriC 的非编码染色体序列相互作用，改变 DnaA 的核苷酸结合状态。因此，尽管 DnaA 是起始复制的关键蛋白，但其他 DNA 结合蛋白不仅在 oriC 上作用以调节其活性，而且在其他调节位点上作用以控制 DnaA 的核苷酸结合状态。在这里，我们回顾了关键 DNA 结合蛋白对大肠杆菌细胞中染色体复制的紧密调控的贡献。
