Folding‐upon‐Repair DNA Nanoswitches for Monitoring the Activity of DNA Repair Enzymes
Copyright policy )Folding‐upon‐Repair DNA Nanoswitches for Monitoring the Activity of DNA Repair Enzymes
AbstractWe present a new class of DNA‐based nanoswitches that, upon enzymatic repair, could undergo a conformational change mechanism leading to a change in fluorescent signal. Such folding‐upon‐repair DNA nanoswitches are synthetic DNA sequences containing O6‐methyl‐guanine (O6‐MeG) nucleobases and labelled with a fluorophore/quencher optical pair. The nanoswitches are rationally designed so that only upon enzymatic demethylation of the O6‐MeG nucleobases they can form stable intramolecular Hoogsteen interactions and fold into an optically active triplex DNA structure. We have first characterized the folding mechanism induced by the enzymatic repair activity through fluorescent experiments and Molecular Dynamics simulations. We then demonstrated that the folding‐upon‐repair DNA nanoswitches are suitable and specific substrates for different methyltransferase enzymes including the human homologue (hMGMT) and they allow the screening of novel potential methyltransferase inhibitors.
- National Research Council Italy
- University of California, San Francisco United States
- National Academies of Sciences, Engineering, and Medicine United States
- Institute of Biosciences and Bioresources Italy
- University of California, Riverside United States
Settore CHIM/01 - CHIMICA ANALITICA, DNA Repair, 1.1 Normal biological development and functioning, DNA nanoswitche, 612, Molecular Dynamics Simulation, triplex DNA, conformational change mechanism, O(6)-Methylguanine-DNA Methyltransferase, Underpinning research, Genetics, Humans, Nanotechnology, DNA nanotechnology, DNA repair enzyme, Organic Chemistry, conformational change mechanism; DNA nanoswitches; DNA nanotechnology; DNA repair enzymes; triplex DNA; DNA; DNA Repair; Humans; Molecular Dynamics Simulation; Nucleic Acid Conformation; O(6)-Methylguanine-DNA Methyltransferase; Nanotechnology, DNA nanoswitches, DNA, DNA nanoswitches; DNA nanotechnology; DNA repair enzymes; conformational change mechanism; triplex DNA; DNA; DNA Repair; Humans; Molecular Dynamics Simulation; Nucleic Acid Conformation; O(6)-Methylguanine-DNA Methyltransferase; Nanotechnology, DNA repair enzymes, Chemical Sciences, Nucleic Acid Conformation, Generic health relevance, Human, conformational change mechanism;
Settore CHIM/01 - CHIMICA ANALITICA, DNA Repair, 1.1 Normal biological development and functioning, DNA nanoswitche, 612, Molecular Dynamics Simulation, triplex DNA, conformational change mechanism, O(6)-Methylguanine-DNA Methyltransferase, Underpinning research, Genetics, Humans, Nanotechnology, DNA nanotechnology, DNA repair enzyme, Organic Chemistry, conformational change mechanism; DNA nanoswitches; DNA nanotechnology; DNA repair enzymes; triplex DNA; DNA; DNA Repair; Humans; Molecular Dynamics Simulation; Nucleic Acid Conformation; O(6)-Methylguanine-DNA Methyltransferase; Nanotechnology, DNA nanoswitches, DNA, DNA nanoswitches; DNA nanotechnology; DNA repair enzymes; conformational change mechanism; triplex DNA; DNA; DNA Repair; Humans; Molecular Dynamics Simulation; Nucleic Acid Conformation; O(6)-Methylguanine-DNA Methyltransferase; Nanotechnology, DNA repair enzymes, Chemical Sciences, Nucleic Acid Conformation, Generic health relevance, Human, conformational change mechanism;
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