MCB Seminar Series: Dynamics of Guanine Quadruplexes

Dr. Anthony Mittermaier, professor and interim dean of students in the Department of Chemistry at McGill University, will present Dynamics of Guanine Quadruplexes. 

Intramolecular guanine quadruplexes (G4s) are non-canonical nucleic acid structures formed by four guanine (G)-rich tracts that assemble into a core of stacked planar tet- rads. G4-forming DNA sequences are enriched in gene promoters and are implicated in the control of gene expression and DNA replication. Consequently, there is great interest in targeting G4s with small molecules, particularly as cancer therapeutics. It is often assumed that human G4s adopt a single, "biologically relevant" conformation in cells. However, it is becoming increasingly clear that G4s are highly dynamic, both in terms of their structures and their interactions with ligands. Our lab is interested in quantifying these dynamics and elucidating how they impact G4 folding and biological function. We have found that the ability of the same stretch of DNA to adopt a multitude of different G4 conformations is extremely common in nature and can profoundly affect the rates of folding and stabilities of the structures. Subtle differences in conformation can also have large impacts on the ability of a polymerase to use G4 DNA as a template, as during transcription or replication. As well, we have used high field NMR spectroscopy to show that G4/ligand dynamics are more complicated than simple association/dissociation, and instead are dominated by ligands transferring directly between stretches of DNA, with implications for the design of G4-targetting therapeutics.

All are welcome to attend. Light refreshments will be served.