G4 Resolvase 1 Binds Both DNA and RNA Tetramolecular Quadruplex with High Affinity and Is the Major Source of Tetramolecular Quadruplex G4-DNA and G4-RNA Resolving

,respectively,asmeasuredbygelmobilityshiftassay.In competition studies tetramolecular RNA quadruplex struc-turesinhibitedtetramolecularDNAquadruplexstructurereso-lution by G4R1/RHAU more efficiently than tetramolecularDNA quadruplex structures inhibited tetramolecular RNAquadruplex structure resolution. Down-regulation of G4R1/RHAUinHeLaT-RExcellsbydoxycycline-inducibleshorthair-pinRNAcausedan8-foldlossofRNAandDNAtetramolecularquadruplexresolution,consistentwithG4R1/RHAUrepresent-ing the major tetramolecular quadruplex helicase activity forboth RNA and DNA structures in HeLa cells. This study dem-onstratesforthefirsttimetheRNAquadruplexresolvingenzy-matic activity associated with G4R1/RHAU and its exceptionalbinding affinity, suggesting a potential novel role for G4R1/RHAU in targeting