Escherichia coli DNA polymerase I can disrupt G‐quadruplex structures during DNA replication
Escherichia coli DNA polymerase I can disrupt G‐quadruplex structures during DNA replication
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DOI：
10.1111/febs.14290
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发表时间：
2017-12
期刊：
影响因子：
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通讯作者：
Fangyuan Teng;Xi-Miao Hou;S. Fan;S. Réty;Shuoxing Dou;X. Xi
中科院分区：
文献类型：
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作者：
Fangyuan Teng;Xi-Miao Hou;S. Fan;S. Réty;Shuoxing Dou;X. Xi
非规范的四链G-四链(G4)DNA结构可以形成广泛分布于整个基因组的富含G的序列。G4结构的存在会阻碍复制聚合酶(POL)的进程，从而损害DNA的复制，如果不能解决这些结构，可能会导致遗传不稳定。在本研究中，我们结合了不同的方法来解决大肠杆菌Pol I是否以及如何解决DNA复制和/或修复过程中的G4障碍的问题。我们发现，在低蛋白质浓度下，大肠杆菌Pol I催化的DNA合成可以被G4结构抑制，并且抑制程度强烈地依赖于G4结构的稳定性。有趣的是，在高蛋白浓度下，E.ColiPol I能够在没有其他分子参与的情况下克服某些G4障碍，并能够实现G4 DNA的完全复制。机制研究表明，多个Pol I蛋白可能参与了G4的展开，而G4结构的破坏需要dNTP水解所产生的能量。本工作不仅揭示了大肠杆菌Pol I的一个未实现的功能，而且提出了一种可能的机制，即在大肠杆菌DNA复制和/或修复过程中G4结构可以被解析。
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.