25-30 August 2019
Henry Ford Building
Europe/Berlin timezone

Guanine-rich DNA regions and their amazing structures

29 Aug 2019, 16:10
35m
Lecture Hall B (Henry Ford Building)

Lecture Hall B

Henry Ford Building

Invited talk Biological applications Biomolecules

Speaker

Prof. Janez Plavec (Slovenian NMR Center, National Institute of Chemistry, Ljubljana, Slovenia, Slovenia)

Description

Double helix is the most known structure of DNA. It can account for transfer of genetic information. However, DNA can fold into a wide range of structures that are associated with its unique biological roles and functions. G-rich DNA segments adopting to d[G≥3N1–7G≥3N1–7G≥3N1–7G≥3] motif are populated in hundreds of thousands and have the potential to form a G-quadruplex structure. G-rich fragments from the PLEKHG3 gene can form tetrahelical structures that differ significantly from G-quadruplexes, despite containing the G-quadruplex folding motif d[G3NG3NG3NG3], where N=AGCGA. These sequences adopt tetrahelical cores of AGCGA repeats, connected with edge-type loops of G–G base pairs. A marked difference between G- and AGCGA-quadruplexes is their opposing response to changes in water activity. While the former become stabilized with decreasing water activity, the reverse is true for the latter (and B-DNA).
Another intriguing case when relying on sequence details alone to predict G-quadruplex structure was reported recently on a G-rich sequence found in the regulatory region of the RANKL gene, associated with homeostasis of bone metabolism. An oligonucleotide with four G-tracts of three successive guanine residues folds into a two-quartet basket-type G-quadruplex.
d[(G4C2)3G4] implicated in neurological disorders ALS and FTD forms two major G-quadruplex structures. Structural characterization of the G-quadruplex named AQU revealed an antiparallel fold composed of four G-quartets and three lateral C–C loops. Two C•C base pairs are stacked on the nearby G-quartet and are involved in a dynamic equilibrium between symmetric N3-amino and carbonyl-amino geometries and protonated C+•C state.

Selected references: Angew. Chem. Int. Ed. 2019, 58, 2387. Angew. Chem. Int. Ed. 2018, 57, 15395. Nucleic Acids Res. 2018, 46, 11605. Nucleic Acids Res. 2019, 47, 2641. J. Am. Chem. Soc. 2019, 141, 2594. Nucleic Acids Res. 2018, 46, 4301. J. Am. Chem. Soc. 2018, 140, 5774.

Primary author

Prof. Janez Plavec (Slovenian NMR Center, National Institute of Chemistry, Ljubljana, Slovenia, Slovenia)

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