Asymmetric base pair opening drives helicase unwinding dynamics (dataset)

The opening of a Watson-Crick double helix is required for crucial cellular processes, including replication, repair and transcription. It has long been assumed that RNA or DNA base pairs are broken by the concerted symmetric movement of complementary nucleobases. By analyzing thousands of base-pair opening and closing events from molecular simulations, here we uncover a systematic stepwiseprocessdrivenbytheasymmetricflipping-outprobability of paired nucleobases. We demonstrate experimentally that such asymmetry strongly biases the unwinding efficiency of DNA helicases towards substrates that bear highly-dynamic nucleobases, such as pyrimidines, on the displaced strand. Duplex substrates with identical thermodynamic stability are thus shown to be more easilyunwoundfromonesidethantheother,inaquantifiableand predictable manner. Our results indicate a possible layer of gene regulation coded in the direction-dependent unwindability of the double helix.