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Structure of Human Telomeric DNA in Crowded Solution
Abstract
G-quadruplex structures formed by DNA at the human telomeres are attractive anticancer targets. Human telomeric sequences can adopt a diverse range of intramolecular G-quadruplex conformations: a parallel-stranded conformation was observed in the crystalline state, while at least four other forms were seen in K(+) solution, raising the question of which conformation is favored in crowded cellular environment. Here, we report the first NMR structure of a human telomeric G-quadruplex in crowded solution. We show that four different G-quadruplex conformations are converted to a propeller-type parallel-stranded G-quadruplex in K(+)-containing crowded solution due to water depletion. This study also reveals the formation of a new higher-order G-quadruplex structure under molecular crowding conditions. Our molecular dynamics simulations of solvent distribution provide insights at molecular level on the formation of parallel-stranded G-quadruplex in environment depleted of water. These results regarding human telomeric DNA can be extended to oncogenic promoters and other genomic G-rich sequences.
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Metadata
- Authors
- Heddi, B., & Phan, A. T.
- Venue
- Journal of the American Chemical Society
- Publisher
- American Chemical Society (ACS)
- Published
- 2011-06-06
- Volume
- 133
- Issue
- 25
- Pages
- 9824-9833
- ISSN
- 0002-7863 (ISSN-L)
- 1520-5126
- OpenAlex
- W1998085469
- Cited by
- 366
- References
- 42
- FWCI
- 14.58
- Type
- journal article
- Language
- en
- Open access
- closed
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