smFRET reveals DHX36 repetitive binding,not unfolding,of G-quadruplexes

Our data challenge Chen et al.'s interpretation of smFRET results, i.e. the repetitive unfolding of G4 with one-base translocations. We believe that the observed oscillatory curve represents the alternate binding of DHX36 to the 3' and 5'G-tetrad of G4s, rather than the repetitive unfolding between the canonical and the transformed non-canonical G4s. Noteworthily, our results reported here also call into question the previously published smFRET data of helicase-mediated G4 unfolding. Therefore,discriminating the smFRET signal of repetitive binding from that of unfolding is very important to avoid misinterpreting smFRET results.