Łazowski Krystian, Woodgate Roger, Fijalkowska Iwona J
Laboratory of DNA Replication and Genome Stability, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawinskiego 5a, 02-106 Warsaw, Poland.
Laboratory of Genomic Integrity, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-3371, United States.
FEMS Microbiol Rev. 2024 Jun 20;48(4). doi: 10.1093/femsre/fuae018.
Research on Escherichia coli DNA replication paved the groundwork for many breakthrough discoveries with important implications for our understanding of human molecular biology, due to the high level of conservation of key molecular processes involved. To this day, it attracts a lot of attention, partially by virtue of being an important model organism, but also because the understanding of factors influencing replication fidelity might be important for studies on the emergence of antibiotic resistance. Importantly, the wide access to high-resolution single-molecule and live-cell imaging, whole genome sequencing, and cryo-electron microscopy techniques, which were greatly popularized in the last decade, allows us to revisit certain assumptions about the replisomes and offers very detailed insight into how they work. For many parts of the replisome, step-by-step mechanisms have been reconstituted, and some new players identified. This review summarizes the latest developments in the area, focusing on (a) the structure of the replisome and mechanisms of action of its components, (b) organization of replisome transactions and repair, (c) replisome dynamics, and (d) factors influencing the base and sugar fidelity of DNA synthesis.
由于所涉及的关键分子过程具有高度保守性，大肠杆菌DNA复制的研究为许多突破性发现奠定了基础，这些发现对我们理解人类分子生物学具有重要意义。直到今天，它仍然备受关注，部分原因在于它是一种重要的模式生物，还因为了解影响复制保真度的因素可能对抗生素耐药性的出现研究很重要。重要的是，在过去十年中得到广泛普及的高分辨率单分子和活细胞成像、全基因组测序以及冷冻电子显微镜技术，使我们能够重新审视关于复制体的某些假设，并对它们的工作方式提供非常详细的见解。对于复制体的许多部分，逐步机制已经得到重构，并且一些新的参与者也已被识别。本综述总结了该领域的最新进展，重点关注：（a）复制体的结构及其组成部分的作用机制；（b）复制体交易与修复的组织；（c）复制体动力学；以及（d）影响DNA合成碱基和糖保真度的因素。
