SignificanceDNA and RNA deformations play crucial roles in biological processes, such as DNA packaging and nucleic acid recognition by proteins. The relevant understanding is limited due to the challenge in the precise measurement of nucleic acid deformations and the complexity of nucleic acid interactions. We solve these two issues using experiments, simulations, and theory. Magnetic tweezers experiments provide an excellent opportunity to precisely measure DNA and RNA twist changes induced by salt, temperature change, and stretching. Surprisingly, our simulations and theory find that common deformation pathways drive DNA and RNA deformations induced by different stimuli. Furthermore, the common deformation pathways appear to be utilized by protein binding to reduce the energy cost of DNA and RNA deformations.