富含鸟嘌呤的DNA序列可以折叠成稳定的四链结构，被称为G四链体或G4。过去十年的研究表明，G4结构在基因组中广泛存在，并且在活跃转录基因的调控区域中普遍存在。G4的形成与基因表达调控和基因组维持等重要生物过程密切相关。然而，它们也可能对基因组完整性造成严重威胁，尤其是通过阻碍DNA复制，G4相关的体细胞突变在癌症基因组中被发现积累。能够解析G4结构的特殊DNA解旋酶和单链DNA结合蛋白在预防基因组不稳定性中起关键作用。大量各种解开G4结构的蛋白表明存在多种G4解析机制在细胞中。最近，在我们对G4如何在DNA复制过程中解析方面取得了相当大的进展。在本综述中，我们首先讨论了当前对基因组G4景观的认识以及G4结构对DNA复制和基因组完整性的影响。然后描述了解析G4结构及其生理意义方面的最新进展。最后，我们讨论了针对G4结构的治疗机会。版权所有©2023作者，Elsevier B.V.出版，保留所有权利。

Guanine-rich DNA sequences can fold into stable four-stranded structures called G-quadruplexes or G4s. Research in the past decade demonstrated that G4 structures are widespread in the genome and prevalent in regulatory regions of actively transcribed genes. The formation of G4s has been tightly linked to important biological processes including regulation of gene expression and genome maintenance. However, they can also pose a serious threat to genome integrity especially by impeding DNA replication, and G4-associated somatic mutations have been found accumulated in the cancer genomes. Specialised DNA helicases and single stranded DNA binding proteins that can resolve G4 structures play a crucial role in preventing genome instability. The large variety of G4 unfolding proteins suggest the presence of multiple G4 resolution mechanisms in cells. Recently, there has been considerable progress in our detailed understanding of how G4s are resolved, especially during DNA replication. In this review, we first discuss the current knowledge of the genomic G4 landscapes and the impact of G4 structures on DNA replication and genome integrity. We then describe the recent progress on the mechanisms that resolve G4 structures and their physiological relevance. Finally, we discuss therapeutic opportunities to target G4 structures.Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.