Department of Oncology, Hematology, Rheumatology and Immune-Oncology, University Hospital Bonn, 53127 Bonn, Germany.
Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, VIC 3010, Australia.
Int J Mol Sci. 2021 Nov 22;22(22):12599. doi: 10.3390/ijms222212599.
DNA molecules can adopt a variety of alternative structures. Among these structures are G-quadruplex DNA structures (G4s), which support cellular function by affecting transcription, translation, and telomere maintenance. These structures can also induce genome instability by stalling replication, increasing DNA damage, and recombination events. G-quadruplex-driven genome instability is connected to tumorigenesis and other genetic disorders. In recent years, the connection between genome stability, DNA repair and G4 formation was further underlined by the identification of multiple DNA repair proteins and ligands which bind and stabilize said G4 structures to block specific DNA repair pathways. The relevance of G4s for different DNA repair pathways is complex and depends on the repair pathway itself. G4 structures can induce DNA damage and block efficient DNA repair, but they can also support the activity and function of certain repair pathways. In this review, we highlight the roles and consequences of G4 DNA structures for DNA repair initiation, processing, and the efficiency of various DNA repair pathways.
DNA 分子可以采用多种替代结构。这些结构包括 G-四链体 DNA 结构 (G4s)，它们通过影响转录、翻译和端粒维持来支持细胞功能。这些结构还可以通过阻碍复制、增加 DNA 损伤和重组事件来诱导基因组不稳定。G-四链体驱动的基因组不稳定性与肿瘤发生和其他遗传疾病有关。近年来，通过鉴定多种与 G4 形成结合并稳定 G4 结构以阻断特定 DNA 修复途径的 DNA 修复蛋白和配体，进一步强调了基因组稳定性、DNA 修复和 G4 形成之间的联系。G4 对不同 DNA 修复途径的相关性很复杂，取决于修复途径本身。G4 结构可以诱导 DNA 损伤并阻止有效的 DNA 修复，但它们也可以支持某些修复途径的活性和功能。在这篇综述中，我们强调了 G4 DNA 结构在 DNA 修复起始、加工和各种 DNA 修复途径效率方面的作用和后果。
