Spiegel Jochen, Adhikari Santosh, Balasubramanian Shankar
Cancer Research UK, Cambridge Institute, Li Ka Shing Centre, Cambridge CB2 0RE, UK.
Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, UK.
Trends Chem. 2020 Feb;2(2):123-136. doi: 10.1016/j.trechm.2019.07.002.
Guanine-rich DNA sequences can fold into four-stranded, noncanonical secondary structures called G-quadruplexes (G4s). G4s were initially considered a structural curiosity, but recent evidence suggests their involvement in key genome functions such as transcription, replication, genome stability, and epigenetic regulation, together with numerous connections to cancer biology. Collectively, these advances have stimulated research probing G4 mechanisms and consequent opportunities for therapeutic intervention. Here, we provide a perspective on the structure and function of G4s with an emphasis on key molecules and methodological advances that enable the study of G4 structures in human cells. We also critically examine recent mechanistic insights into G4 biology and protein interaction partners and highlight opportunities for drug discovery.
富含鸟嘌呤的DNA序列可以折叠成称为G-四链体（G4s）的四链非经典二级结构。G4s最初被认为是一种结构上的奇特现象，但最近的证据表明它们参与了关键的基因组功能，如转录、复制、基因组稳定性和表观遗传调控，并且与癌症生物学有许多联系。总的来说，这些进展激发了对G4机制的研究以及随之而来的治疗干预机会。在这里，我们提供了关于G4s结构和功能的观点，重点关注能够研究人类细胞中G4结构的关键分子和方法学进展。我们还批判性地审视了最近对G4生物学和蛋白质相互作用伙伴的机制见解，并强调了药物发现的机会。
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