Regeneration of Burnt Bridges on a DNA Catenane Walker

• Published in: Angewandte Chemie International Edition 2020-09, Vol.59 (38), p.16366-16370
• Main Authors: Valero, Julián, Famulok, Michael
• Format: Article
• Language: English
• Subjects: Bacteriophage T7 - enzymology; biohybrids; Bridges; Communication; Communications; Deoxyribonucleic acid; DNA; DNA catenane walkers; DNA nanotechnology; DNA, Catenated - chemistry; DNA, Catenated - genetics; DNA-directed RNA polymerase; DNA-Directed RNA Polymerases - chemistry; Energy sources; Molecular machines; Nanotechnology - methods; Nucleic Acid Hybridization; Regeneration; Ribonuclease, Pancreatic - chemistry; Ribonucleic acid; RNA; RNA - chemistry; RNA - genetics; Structure-function relationships; Viral Proteins - chemistry
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.202004447

DNA walkers are molecular machines that can move with high precision onthe nanoscale due to their structural and functional programmability. Despite recent advances in the field that allow exploring different energy sources, stimuli, and mechanisms of action for these nanomachines, the continuous operation and reusability of DNA walkers remains challenging because in most cases the steps, once taken by the walker, cannot be taken again. Herein we report the path regeneration of a burnt‐bridges DNA catenane walker using RNase A. This walker uses a T7RNA polymerase that produces long RNA transcripts to hybridize to the path and move forward while the RNA remains hybridized to the path and blocks it for an additional walking cycle. We show that RNA degradation triggered by RNase A restores the path and returns the walker to the initial position. RNase inhibition restarts the function of the walker. Making burnt bridges passable: A burnt‐bridges DNA walker that employs long RNA transcripts for moving along steps on a DNA‐nanotube path, can operate continuously when an enzymatic strategy is employed which consists of degrading the RNA that block the path through addition of RNase A and subsequently restarting the walking through the use of an RNA inhibitor.