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Force-Dependent Behaviour of Non-Standard DNA Structures and their Uses in Artificial DNA Machines and in Genetic Regulation

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Dynamic states of the DNA molecule

At the level of individual molecules, forces that are relatively unimportant at the larger macroscopic scale can become crucial. This applies across the sciences – from the realms of physics to the regulation of DNA transcription.

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For all structures composed of nanometre-sized units, thermal motion and disturbances in the low range of the picoNewton, a trillionth of a Newton, make a profound difference. The EU-funded FDBNSDNA (Force-dependent behaviour of non-standard DNA structures and their uses in artificial DNA machines and in genetic regulation) project has made it possible to ascertain the effects of the thermal background on DNA structures. Particularly applicable to the interaction of DNA with regulatory proteins, the researchers worked with an eye on novel non-standard DNA structures based on guanine, poly-guanine structures or G-complexes. These show potential as building blocks for future molecular-scaled devices and are rife in the human genome at the telomeres with biological significance such as ageing and drug targets. FDBNSDNA has improved the design of a massively parallel centrifugal force microscope to collect data on motion, folding and unfolding of many DNA structures at the same time. These features are crucial for molecular interaction. The researchers also optimised sample preparation techniques to exploit the full potential of the microscope. Applications for in-depth knowledge of the physical properties of non-standard DNA structures extend to molecular-scaled devices and electronics. As physical properties determine the ability of molecules to interact and regions containing G-complexes are involved with ageing-associated diseases including cancer, the research could have a big impact on healthcare.

Keywords

Molecules, FDBNSDNA, DNA structures, G-complexes, electronics

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