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首页> 外文期刊>The FEBS journal >Escherichia coli DNA polymerase I can disrupt G-quadruplex structures during DNA replication
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Escherichia coli DNA polymerase I can disrupt G-quadruplex structures during DNA replication

机译:大肠杆菌DNA聚合酶I可以破坏DNA复制期间的G-QuadrepleS结构

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摘要

Non-canonical four-stranded G-quadruplex (G4) DNA structures can form in G-rich sequences that are widely distributed throughout the genome. The presence of G4 structures can impair DNA replication by hindering the progress of replicative polymerases (Pols), and failure to resolve these structures can lead to genetic instability. In the present study, we combined different approaches to address the question of whether and how Escherichia coli Pol I resolves G4 obstacles during DNA replication and/or repair. We found that E. coli Pol I-catalyzed DNA synthesis could be arrested by G4 structures at low protein concentrations and the degree of inhibition was strongly dependent on the stability of the G4 structures. Interestingly, at high protein concentrations, E. coli Pol I was able to overcome some kinds of G4 obstacles without the involvement of other molecules and could achieve complete replication of G4 DNA. Mechanistic studies suggested that multiple Pol I proteins might be implicated in G4 unfolding, and the disruption of G4 structures requires energy derived from dNTP hydrolysis. The present work not only reveals an unrealized function of E. coli Pol I, but also presents a possible mechanism by which G4 structures can be resolved during DNA replication and/or repair in E. coli.
机译:非规范的四链G- Quadreplex(G4)DNA结构可以在富含G的序列中形成,其在整个基因组中广泛分布。 G4结构的存在可以通过阻碍重复聚合酶(POL)的进展来损害DNA复制,并且未能解决这些结构可能导致遗传不稳定。在本研究中,我们组合了不同的方法来解决在DNA复制和/或修复期间eScherichia Coli Pol I如何解决G4障碍的问题。我们发现大肠杆菌Pol I催化的DNA合成可以通过低蛋白质浓度的G4结构被捕,并且抑制程度强烈取决于G4结构的稳定性。有趣的是,在高蛋白质浓度下,大肠杆菌POL我能够克服某些类型的G4障碍而不涉及其他分子,可以实现G4 DNA的完全复制。机械研究表明,多个POL I蛋白可能涉及G4展开,并且G4结构的破坏需要衍生自DNTP水解的能量。目前的工作不仅揭示了大肠杆菌POL I的未实现功能,而且还提出了在大肠杆菌的DNA复制和/或修复期间可以解决G4结构的可能机制。

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