G4 Quadruplex Recognition in the Human DEAH-Box Helicase RHAU

Abstract

G4 quadruplexes of nucleic acids are very stable stacks of four guanylates that are associated in co-planar fashion via hydrogen bonds. Monovalent cations such as potassium or sodium are bound in the center of the quartet of guanyl groups. G4 quadruplexes can only be unwound enzymatically in vivo and this requires an energy source like ATP. G4 quadruplexes provide therefore the means to regulate nucleic acid specific cellular processes such as telomerase activity or gene expression. The recently discovered DEAH-box helicase RHAU, also known as DHX36, binds to G4 DNA and RNA quadruplexes and unwinds them. G4 quadruplex recognition occurs in a short stretch of amino acids in the N-terminal domain of RHAU, named “RHAU specific motif”. Using a combination of biophysical methods such as Circular Dichroism, Dynamic Light Scattering, Size Exclusion Chromatography, Analytical Ultracentrifugation, Small Angle X-ray Scattering, Nuclear Magnetic Resonance and X-ray crystallography we are striving to shed light into how RHAU recognizes and binds G4 DNA and RNA complexes.