G-quadruplexes (G4s) are four-stranded nucleic acid structures that form in guanine-rich DNA or RNA. Repeating layers of extensively hydrogen bonded guanine-quartets coordinate a cationic core and stack upon one another to create extremely stable G4 structures. Although these structures have been studied in vitro for decades, in vivo roles have only recently been appreciated. G4s are best known as blockades that can disrupt essential processes, including transcription, translation, and replication. However, G4s also have positive roles, particularly in gene expression, chromosome end protection, pathogenesis, and radiation resistance. This duality implies that cells have evolved mechanisms to ensure proper G4 homeostasis by regulating formation and unwinding of G4s and repair of damage that results from G4s.
Above is a figure depicting our work studying the role of prokaryotic DNA G4s. The manuscript describes a guanine-specific pocket (GSP) of the bacterial RecQ helicase that facilitates G4-specific unwinding. (Voter et al. (2018) Nature Comm.)
Our lab is investigating the mechanisms by which G4 nucleic acids are processed at mechanistic and cellular levels. We are using structural and biochemical systems to understand how helicases and other enzymes can unwind G4 structures in vitro. We are also using and genetic approaches to identify cellular mechanisms that play roles in G4 processing.