期刊
NUCLEIC ACIDS RESEARCH
卷 42, 期 12, 页码 8106-8114出版社
OXFORD UNIV PRESS
DOI: 10.1093/nar/gku464
关键词
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资金
- American Cancer Society [RSG-12-066-01-DMC]
- National Institutes of Health (NIH) [1DP2GM105453]
- Human Frontier Science Program [RGP0007/2012]
- U.S. National Science Foundation Physics Frontiers Center Program through the Center for the Physics of Living Cells [0822613]
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [DP2GM105453] Funding Source: NIH RePORTER
The quadruplex forming G-rich sequences are unevenly distributed throughout the human genome. Their enrichment in oncogenic promoters and telomeres has generated interest in targeting G-quadruplex (GQ) for an anticancer therapy. Here, we present a quantitative analysis on the conformations and dynamics of GQ forming sequences measured by single molecule fluorescence. Additionally, we relate these properties to GQ targeting ligands and G4 resolvase 1 (G4R1) protein binding. Our result shows that both the loop (non-G components) length and sequence contribute to the conformation of the GQ. Real time single molecule traces reveal that the folding dynamics also depend on the loop composition. We demonstrate that GQ-stabilizing small molecules, N-methyl mesoporphyrin IX (NMM), its analog, NMP and the G4R1 protein bind selectively to the parallel GQ conformation. Our findings point to the complexity of GQ folding governed by the loop length and sequence and how the GQ conformation determines the small molecule and protein binding propensity.
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