Dienstag, 22. November 2016, 14:00 - 15:30 iCal
Prof. Jean-Louis Mergny
Universität Bordeaux
"Quadruplexes are everywhere"
Hörsaal 4 der Fakultät für Chemie
Währinger Straße 42, 1090 Wien
Vortrag
Quadruplexes are Everywhere!
Jean-Louis Mergny
Université de Bordeaux – Inserm U1212 – CNRS UMR 5320
European Institute of Chemistry and Biology (IECB), France. Jean-louis.mergny@inserm.fr
“DNA comes in many forms” (A. Rich): a number of non-classical pairing patterns are possible between or within DNA strands. These interactions result in the formation of unusual structures, among them the G-quadruplex and the i-motif. G-quadruplexes (G4) result from the stacking of several G-quartets (formed by hydrogen bonding of four coplanar guanines), and are stabilized by monocations such as sodium and potassium. These structures are very stable under physiological conditions but were first thought to be an in vitro anomaly. Critical evidence for the biological relevance of G4 has come from use of G4-specific antibodies and results obtained in a variety of organisms.
We are now using novel strategies, including new analytical tools and a unique model organism, to confirm the importance of G-quadruplexes and study their properties. We first developed a new algorithm for prediction of G4 propensity (1). We developed new assays to identify and analyze selective G4 ligands (2) and the resolution of G4 structures by helicases (3-5). We provide evidence for G4 existence in living cells using in vivo NMR (6). Having established that quadruplex-prone regions are conserved in the genome of viruses, we are currently investigating whether quadruplexes may become the Achilles' Heel of the viral life cycle (7-8).
In addition, besides their importance in Biology, unusual nucleic acid structures may find applications in Biotechnologies and Nanotechnologies. These structures have clear advantages over conventional duplex DNA, such as enhanced thermal stability, conductivity, and sensitivity to chemical stimuli (9). A major drawback of G4 and i-DNA designs is the lack of control over the assembly process. We recently provided solutions to this problem (10-11).
(1) Bedrat et al., Nucleic Acids Res. 2016, 44: 1746
(2) De Rache et al., Biochimie 2015, 115: 194
(3) Mendoza et al., Nucleic Acids Res. 2015, 43: e71
(4) Mendoza et al., Nucleic Acids Res. 2016, 44: 1989
(5) Gueddouda et al., submitted
(6) Salgado et al., Chem. Sci. 2015, 6: 3273
(7) Amrane et al., J. Am. Chem. Soc 2014, 136: 5249
(8) Métifiot et al., Biochimie 2015, 118: 173
(9) Yatsunyk, Mendoza & Mergny., Acc. Chem. Res. 2014, 47: 1836
(10) Mendoza et al., Chem. Eur. J. 2015, 21: 6732
(11) Fu et al., 2016, in preparation
Veranstalter
Kontakt
Brigitte Schwarz
Fakultät für Chemie der Universität Wien
Dekanat
01/4277-52006
brigitte_schwarz@univie.ac.at
Erstellt am Freitag, 18. November 2016, 11:01
Letzte Änderung am Montag, 21. November 2016, 09:10