Grün J Tassilo, Blümler Anja, Burkhart Ines, Wirmer-Bartoschek Julia, Heckel Alexander, Schwalbe Harald
Institute for Organic Chemistry and Chemical Biology, Goethe University Frankfurt am Main, Frankfurt 60323, Germany.
Center of Biomolecular Magnetic Resonance (BMRZ), Goethe University Frankfurt am Main, Frankfurt 60323, Germany.
J Am Chem Soc. 2021 Apr 28;143(16):6185-6193. doi: 10.1021/jacs.1c01089. Epub 2021 Apr 19.
The folding of DNA G-quadruplexes (G4) is essential to regulate expression of oncogenes and involves polymorphic long-lived intermediate states. G4 formation requires four G-tracts, but human gene-promoters often contain multiple G-tracts that act as . These additional G-tracts are highly conserved and add multiple layers of functional complexity, as they are crucial to maintain G4 function after oxidative damage. Herein, we unravel the folding dynamics of the G4 sequence containing five G-tracts from , the major proliferation-driving oncogene. We devise a general method to induce folding at constant experimental conditions using a photochemical trapping strategy. Our data dissect the individual kinetics and thermodynamics of the mechanism of -G4.
DNA G-四链体（G4）的折叠对于调控癌基因的表达至关重要，且涉及多态性的长寿命中间状态。G4的形成需要四个鸟嘌呤富集区（G- tracts），但人类基因启动子通常含有多个起作用的G- tracts。这些额外的G- tracts高度保守，并增加了功能复杂性的多个层面，因为它们对于氧化损伤后维持G4功能至关重要。在此，我们揭示了来自主要增殖驱动癌基因的包含五个G- tracts的G4序列的折叠动力学。我们设计了一种通用方法，使用光化学捕获策略在恒定实验条件下诱导折叠。我们的数据剖析了 -G4机制的个体动力学和热力学。
