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

TL;DR

This study uses smFRET to show that DHX36 binds repeatedly to G-quadruplexes without unfolding them, challenging previous interpretations of G4 unfolding mechanisms.

Contribution

It provides new insights into DHX36-G4 interactions, emphasizing binding behavior over unfolding, and questions prior smFRET interpretations of G4 dynamics.

Findings

DHX36 binds repeatedly to G4s without unfolding

Repetitive binding explains oscillatory smFRET signals

Challenges previous interpretations of G4 unfolding in smFRET studies

Abstract

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.