Michel Bénédicte, Sandler Steven J
Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Université Paris-Sud, Université Paris-Saclay, Gif-sur-Yvette, France
Department of Microbiology, University of Massachusetts at Amherst, Amherst, Massachusetts, USA
J Bacteriol. 2017 Jun 13;199(13). doi: 10.1128/JB.00102-17. Print 2017 Jul 1.
In bacteria, replication forks assembled at a replication origin travel to the terminus, often a few megabases away. They may encounter obstacles that trigger replisome disassembly, rendering replication restart from abandoned forks crucial for cell viability. During the past 25 years, the genes that encode replication restart proteins have been identified and genetically characterized. In parallel, the enzymes were purified and analyzed , where they can catalyze replication initiation in a sequence-independent manner from fork-like DNA structures. This work also revealed a close link between replication and homologous recombination, as replication restart from recombination intermediates is an essential step of DNA double-strand break repair in bacteria and, conversely, arrested replication forks can be acted upon by recombination proteins and converted into various recombination substrates. In this review, we summarize this intense period of research that led to the characterization of the ubiquitous replication restart protein PriA and its partners, to the definition of several replication restart pathways , and to the description of tight links between replication and homologous recombination, responsible for the importance of replication restart in the maintenance of genome stability.
在细菌中,在复制起点组装的复制叉会移动到终点,终点通常在几兆碱基之外。它们可能会遇到引发复制体解体的障碍,这使得从废弃复制叉重新启动复制对于细胞存活至关重要。在过去25年里,编码复制重新启动蛋白的基因已被鉴定并进行了遗传学特征分析。与此同时,这些酶被纯化并进行了分析,它们能够以与序列无关的方式从叉状DNA结构催化复制起始。这项工作还揭示了复制与同源重组之间的紧密联系,因为从重组中间体重新启动复制是细菌中DNA双链断裂修复的一个关键步骤,反之,停滞的复制叉可被重组蛋白作用并转化为各种重组底物。在这篇综述中,我们总结了这一密集的研究阶段,该阶段导致了普遍存在的复制重新启动蛋白PriA及其伙伴的特征描述、几种复制重新启动途径的定义以及对复制与同源重组之间紧密联系的描述,这些联系解释了复制重新启动在维持基因组稳定性中的重要性。