DHX36 is a eukaryotic DEAH/RHA family helicase that disrupts G-quadruplex 
structures (G4s) with high specificity, contributing to regulatory roles of G4s. 
Here we used a DHX36 truncation to examine the roles of the 13-amino acid 
DHX36-specific motif (DSM) in DNA G4 recognition and disruption. We found that 
the DSM promotes G4 recognition and specificity by increasing the G4 binding 
rate of DHX36 without affecting the dissociation rate. Further, for most of the 
G4s measured, the DSM has little or no effect on the G4 disruption step by 
DHX36, implying that contacts with the G4 are maintained through the transition 
state for G4 disruption. This result suggests that partial disruption of the G4 
from the 3' end is sufficient to reach the overall transition state for G4 
disruption, while the DSM remains unperturbed at the 5' end. Interestingly, the 
DSM does not contribute to G4 binding kinetics or thermodynamics at low 
temperature, indicating a highly modular function. Together, our results animate 
recent DHX36 crystal structures, suggesting a model in which the DSM recruits 
G4s in a modular and flexible manner by contacting the 5' face early in binding, 
prior to rate-limiting capture and disruption of the G4 by the helicase core.