Bryan Tracy M
Children's Medical Research Institute, University of Sydney, Westmead, NSW 2145, Australia.
Molecules. 2019 Sep 22;24(19):3439. doi: 10.3390/molecules24193439.
G-quadruplexes are four-stranded guanine-rich structures that have been demonstrated to occur across the genome in humans and other organisms. They provide regulatory functions during transcription, translation and immunoglobulin gene rearrangement, but there is also a large amount of evidence that they can present a potent barrier to the DNA replication machinery. This mini-review will summarize recent advances in understanding the many strategies nature has evolved to overcome G-quadruplex-mediated replication blockage, including removal of the structure by helicases or nucleases, or circumventing the deleterious effects on the genome through homologous recombination, alternative end-joining or synthesis re-priming. Paradoxically, G-quadruplexes have also recently been demonstrated to provide a positive role in stimulating the initiation of DNA replication. These recent studies have not only illuminated the many roles and consequences of G-quadruplexes, but have also provided fundamental insights into the general mechanisms of DNA replication and its links with genetic and epigenetic stability.
G-四链体是富含鸟嘌呤的四链结构，已被证明存在于人类和其他生物体的整个基因组中。它们在转录、翻译和免疫球蛋白基因重排过程中发挥调节功能，但也有大量证据表明，它们会对DNA复制机制构成强大障碍。本综述将总结近期在理解自然界为克服G-四链体介导的复制阻滞而进化出的多种策略方面取得的进展，包括通过解旋酶或核酸酶去除结构，或通过同源重组、替代末端连接或合成重新引发来规避对基因组的有害影响。矛盾的是，G-四链体最近也被证明在刺激DNA复制起始方面发挥积极作用。这些最新研究不仅阐明了G-四链体的多种作用和后果，还为DNA复制的一般机制及其与遗传和表观遗传稳定性的联系提供了基本见解。
