Dr. Janez Plavec

Slovenian NMR Centre,

Slovenian National Institute of Chemistry;

March 2nd, 2018 – Spring Seminar

Time and Location: Noon in Meyerhoff Chemistry, Room 120

Host: Dr. Katherine Seley-Radtke

 

Do G-rich DNA regions only fold into G-quadruplexes?

Guanine- and cytosine-rich sequences may fold into tetrahelical structures called G-quadruplexes and i-motifs under certain conditions, respectively. G-quadruplexes are noncanonical four stranded structures consisting of stacks of guanine residues assembled into G-quartets and coordinated with intercalated cations such as potassium and sodium. These structures exist in dynamic equilibrium within the single-stranded G-rich DNA generated during major genomic events (replication, transcription). G-quadruplexes may be modulators of nucleic-acid-processing proteins and, as such, as potential components of new pathways of genome and epigenome regulation. Solution-state NMR spectroscopy has contributed significant insights that helped to uncover overall topologies and local features of non-B-DNA structural families alone or in interaction with other molecules such as small molecule ligands. An unexpected four-stranded structures stabilized by G-A and G-C base pairs stimulated us to explore if G- and A-rich repeat segments of DNA can adopt tetrahelical structures different from G-quadruplexes. 5′-AGCGA-3′ repeat sequences are found in regulatory regions of 38 different human genes linked to neurodevelopment and neurological disorders, abnormal cartilage and bone formations, cancer and regulation of basic cellular processes. In contrast to the expected G-quartet-based topologies adopted by 5′-GGG-3′ repeats structures are stabilized by G-C, G-A and G-G base pairs that interact to form unique structures. In comparison to G-quadruplexes novel structural family does not show the same sensitivity to the presence of cations. New structures suggest that folding landscapes and structural diversity of DNA oligonucleotides are much more complex than previously assumed.

 

Selected references:

  1. V. Kocman, J. Plavec, Nat. Commun. 2017, 8:15355.
  2. V. Kocman, J. Plavec, Nat. Commun. 2014, 5:5831.
  3. M. Marušič, J. Plavec, Angew. Chem. Int. Ed. 2015, 54, 11716-11719.
  4. M. Gajarský, M. Lenarčič Živković, P. Stadlbauer, B. Pagano, R. Fiala, J. Amato, L. Tomáška, J. Šponer, J. Plavec and L. Trantírek, J. Am. Chem. Soc. 2017, 139, 3591-3594.
  5. M. Laura Greco, A. Kotar, R. Rigo, C. Cristofari, J. Plavec, C. Sissi, Nucleic Acids Res. 2017, 45, 10132.
  6. P. Galer, B. Wang, P. Šket, J. Plavec, Angew. Chem. Int. Ed. 2016, 55, 1993-1997.
  7. A. Kotar, B. Wang, A. Shivalingam, J. Gonzalez-Garcia, R. Vilar, J. Plavec, Angew. Chem. Int. Ed. 2016, 55, 12508-12511.