Doktorské studium

Studijní obor Strukturní biologie

Název práce: Behavior of alternative DNA structures at electrically charged surfaces

Školitel: doc. RNDr. Miroslav Fojta, CSc.

Oficiální zadání:
Electrochemical techniques have been established as sensitive tools for the analysis of nucleic acids structure, suitable not only for disrimination between „native“ (double-stranded) and „denatured“ (single-stranded) DNA, but also for sensitive detection of relatively subtle changes in the DNA conformation, DNA damage or interactions [1,2]. Recently, studies of the behavior of alternative DNA structures such as guanine quadruplexes (G4) [3,4] appeared in the literature [5]. Recent results of the supervisor’s group [6] have indicated that the G4 formation remarkably influences electrochemical responses of relevant oligonucleotides (ON). Within this PhD thesis topic, a systematic study of electrochemical and adsorption/desorption properties of ON involving G-rich segments, suitable for G4 formation, will be pursued. Sequences of the model ON will either derived from natural DNA elements (such as telomeric DNA repeats), or specifically designed for studies of particular phenomena (e.g., effects of the length and nucleobase composition of loops or tails flanking the G4-forming stretches on the structure stability and/or adsorption at the electrode surface). Effects of conditions such as ionic conditions, presence of selected G4-binding ligands etc., will be investigated. Electrochemical measurements will be complemented with CD spectroscopy and electrphoretic studies.

[1] E. Paleček, M. Bartošík, Electrochemistry of Nucleic Acids, Chem Rev 112 (2012) 3427-3481.

[2] M. Hocek, M. Fojta, Nucleobase modification as redox DNA labelling for electrochemical detection, Chem Soc Rev 40 (2011) 5802-5814.

[3] V. Brazda, L. Haronikova, J.C.C. Liao, M. Fojta, DNA and RNA quadruplex-binding proteins, International journal of molecular sciences 15 (2014) 17493-17517.

[4] J. Kypr, I. Kejnovská, D. Renčiuk, M. Vorlíčková, Circular dichroism and conformational polymorphism of DNA, Nucleic Acids Res. 37 (2009) 1713-1725.

[5] A.-M. Chiorcea-Paquim, A.M. Oliveira-Brett, Redox behaviour of G-quadruplexes, Electrochimica Acta 126 (2014) 162-170.

[6] P. Vidláková, H. Pivoňková, I. Kejnovská, L. Trnková, M. Vorlíčková, M. Fojta, L. Havran, G-quadruplex-based structural transitions in 15-mer DNA oligonucleotides varying in lengths of internal oligo(dG) stretches detected by voltammetric techniques, submitted (2015).

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