Observation of Flexibility Reversal in DNA Bending

Several experiments on DNA looping show that DNA looping probability at short length scales is higher than the prediction of the wormlike chain model. This observation suggests that DNA becomes more flexible at large bending angles and hints at the possibility that sequence dependence of flexibility may not be universal across different bending regimes. Using a FRET-based DNA looping assay, we measured flexibilities of various DNA sequences (some of which include base pair mismatches) from the looping and unlooping rates. Surprisingly, we find a strong correlation between the measured looping and unlooping rates, which points to an apparent flexibility reversal: more flexible sequences in the unlooped state are more rigid in the looped state. To explain this counterintuitive finding, we present a few hypotheses that challenge our coarse-grained level understanding of DNA.