期刊
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
卷 143, 期 16, 页码 6185-6193出版社
AMER CHEMICAL SOC
DOI: 10.1021/jacs.1c01089
关键词
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资金
- DFG graduate research program CLiC [GRK 1986]
- state of Hesse
- DFG large-scale equipment funds [280251937]
This study unravels the folding dynamics of a G4 sequence containing five G-tracts from cMYC, a major oncogene, and dissects the individual kinetics and thermodynamics of the spare-tire mechanism of cMYC-G4.
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 spare-tires. 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 cMYC, 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 spare-tire mechanism of cMYC-G4.
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