Revisiting the anomalous bending elasticity of sharply bent DNA

TL;DR

This study uses molecular dynamics simulations to investigate how preexisting nicks influence the bending flexibility of DNA, revealing that nicks facilitate basepair disruption and reduce bending energy, which may explain experimental anomalies.

Contribution

The paper demonstrates that preexisting nicks significantly affect DNA bending flexibility by promoting basepair disruption, offering new insights into DNA mechanics.

Findings

Nicks promote basepair disruption at nicked sites.

Lower temperatures suppress nick-dependent basepair disruption.

Nick-free DNA requires higher bending to induce basepair disruption.

Abstract

Several recent experiments suggest that sharply bent DNA has a surprisingly high bending flexibility, but the cause of this flexibility is poorly understood. Although excitation of flexible defects can explain these results, whether such excitation can occur with the level of DNA bending in these experiments remains unclear. Intriguingly, the DNA contained preexisting nicks in most of these experiments but whether nicks might play a role in flexibility has never been considered in the interpretation of experimental results. Here, using full-atom molecular dynamics simulations, we show that nicks promote DNA basepair disruption at the nicked sites, which drastically reduces DNA bending energy. In addition, lower temperatures suppress the nick-dependent basepair disruption. In the absence of nicks, basepair disruption can also occur but requires a higher level of DNA bending. Therefore, basepair disruption inside B-form DNA can be suppressed if the DNA contains preexisting nicks. Overall, our results suggest that the reported mechanical anomaly of sharply bent DNA is likely dependent on preexisting nicks, therefore the intrinsic mechanisms of sharply bent nick-free DNA remain an open question.