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

Dimerization of DNA G-quadruplexes: an EPR investigation

Not scheduled
4h
Harnack House and Henry Ford Building

Harnack House and Henry Ford Building

Board: 250
Poster Posters

Speaker

Dr Yury Kutin (TU Dortmund)

Description

G-quadruplexes are DNA secondary structures containing stacked guanine tetrads stabilized by central cations. They are formed by self-assembly of guanine-rich oligonucleotides by Hoogsteen base pairing. Studies have shown that G-quadruplexes form in vivo in oncogene regulatory regions and at telomeric ends of chromosomes, thus shortening cancer cell lifetimes [1].

Many G-quadruplex species are known to form higher-order structures like dimers, which are believed to play a crucial role in G-quadruplexes biological activity. This makes the understanding of the structure and formation of these structures an important goal, where the EPR spectroscopy can make a substantial contribution. Recently, rigid CuII-based spin labels were successfully incorporated into biomimetic tetramolecular DNA G-quadruplexes [2]. The potential of the DNA-bound metal spin labels for distance measurements was demonstrated by intramolecular pulsed EPR experiments on CuII ions attached at 3’ and 5’ ends of G-quadruplex monomers [3].

In the present work we use the orientation selective PELDOR (or DEER) and RIDME techniques to derive CuII–CuII distances in various forms of G-quadruplex dimers to gain insight into the topology of these higher-order structures. With the CuII-based spin labels attached at either 3’ or 5’ ends of several G-quadruplex species, the dimerization at the opposite ends was studied.

EPR was also used to probe the dimerization of G-quadruplexes mediated by organic molecules. This provided information on both the resulting structures and the efficiency of the potential dimerization pathways. Interaction of G-quadruplexes with a variety of transition metal complexes makes EPR the method of choice for distance measurements within G-quadruplex-metal complex adducts, providing valuable information on binding modes.

References:
[1] R. Hänsel-Hertsch et al., Nat Rev Mol Cell Biol. 18, 279 (2017).
[2] D. M. Engelhard et al., Angew. Chem. Int. Ed. 52, 12843 (2013).
[3] D. M. Engelhard et al., Chem. Commun. 54, 7455 (2018).

Primary authors

Dr Yury Kutin (TU Dortmund) Mr Lukas Stratmann (TU Dortmund) Prof. Guido Clever ( TU Dortmund) Prof. Müge Kasanmascheff (TU Dortmund)

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