G-quadruplexes (G4s) are tetrahelical DNA structures stabilized by four guanines paired via Hoogsteen hydrogen bonds into quartets. While their presence within eukaryotic DNA is known to play a key role in regulatory processes, their functional mechanisms are still under investigation. In the present work, we analysed the nanomechanical properties of three G4s present within the promoter of the KIT proto-oncogene from a single-molecule point of view through the use of magnetic tweezers (MTs). The study of DNA extension fluctuations under negative supercoiling allowed us to identify a characteristic fingerprint of G4 folding. We further analysed the energetic contribution of G4 to the double-strand denaturation process in the presence of negative supercoiling, and we observed a reduction in the energy required for strands separation. © 2021 The Author(s). Published by Oxford University Press on behalf of Nucleic Acids Research.

Nanomechanics of G-quadruplexes within the promoter of the KIT oncogene

Salerno D.;Vesco G.;Nardo L.;
2021-01-01

Abstract

G-quadruplexes (G4s) are tetrahelical DNA structures stabilized by four guanines paired via Hoogsteen hydrogen bonds into quartets. While their presence within eukaryotic DNA is known to play a key role in regulatory processes, their functional mechanisms are still under investigation. In the present work, we analysed the nanomechanical properties of three G4s present within the promoter of the KIT proto-oncogene from a single-molecule point of view through the use of magnetic tweezers (MTs). The study of DNA extension fluctuations under negative supercoiling allowed us to identify a characteristic fingerprint of G4 folding. We further analysed the energetic contribution of G4 to the double-strand denaturation process in the presence of negative supercoiling, and we observed a reduction in the energy required for strands separation. © 2021 The Author(s). Published by Oxford University Press on behalf of Nucleic Acids Research.
2021
DNA; DNA, Superhelical; Guanine; Kinetics; Nucleic Acid Denaturation; Oncogenes; Promoter Regions, Genetic; Proto-Oncogene Mas; Proto-Oncogene Proteins c-kit; Single Molecule Imaging; G-Quadruplexes
Buglione, E.; Salerno, D.; Marrano, C. A.; Cassina, V.; Vesco, G.; Nardo, L.; Dacasto, M.; Rigo, R.; Sissi, C.; Mantegazza, F.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11383/2133890
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