Modeling Gene Expression Instability by Programmed and Switchable Polymerization/Nicking DNA Nanomachineries

Models for gene expression instability by noncanonical DNA-nanostructures are introduced. The systems consist of a promoter-template scaffold that acts as a polymerization/nicking machinery that models, in the presence of polymerase/Nt.BbvCI and dNTPs, the autonomous synthesis of displaced strands mimicking the native “genes”. Incorporation of noncanonical DNA structures into the scaffolds consisting of Sr2+-ion-stabilized G-quadruplexes, T-A·T triplexes, or ATP–aptamer complexes results in the perturbation of the polymerization/nicking DNA machineries and the synthesis of displaced strands-“genes” exhibiting other structures. By the dissociation of the noncanonical blockage units, the regeneration of the synthesis of the original intact displaced strands-“genes” is demonstrated. The study introduces conceptual means to eliminate destructive gene expression instability pathways.