Folding‐upon‐Repair DNA Nanoswitches for Monitoring the Activity of DNA Repair Enzymes

Autor: Rosanna Mattossovich, Francesco Ricci, Giuseppe Perugino, Nada Farag, Alessandro Porchetta, Giulia Palermo, Rosa Merlo, Łukasz Nierzwicki
Přispěvatelé: Farag, Nada, Mattossovich, Rosanna, Merlo, Rosa, Nierzwicki, Łukasz, Palermo, Giulia, Porchetta, Alessandro, Perugino, Giuseppe, Ricci, Francesco
Rok vydání: 2021
Předmět:
Conformational change
Fluorophore
Methyltransferase
DNA Repair
DNA repair
1.1 Normal biological development and functioning
DNA nanoswitche
Molecular Dynamics Simulation
010402 general chemistry
triplex DNA
01 natural sciences
Article
Catalysis
Nucleobase
03 medical and health sciences
O(6)-Methylguanine-DNA Methyltransferase
conformational change mechanism
chemistry.chemical_compound
Settore CHIM/01
Underpinning research
DNA nanotechnology
Genetics
Humans
Nanotechnology
030304 developmental biology
chemistry.chemical_classification
DNA repair enzyme
0303 health sciences
010405 organic chemistry
Organic Chemistry
DNA nanoswitches
DNA repair enzymes
DNA
Nucleic Acid Conformation
General Medicine
General Chemistry
0104 chemical sciences
Enzyme
chemistry
Chemical Sciences
Biophysics
Generic health relevance
Human
Zdroj: Angewandte Chemie (International ed. in English), vol 60, iss 13
Angew Chem Int Ed Engl
Angewandte Chemie (Int. ed., Print) 60 (2021): 2–9. doi:10.1002/anie.202016223
info:cnr-pdr/source/autori:Nada Farag (1), Rosanna Mattossovich (2), Rosa Merlo (2), ?ukasz Nierzwicki (3), Giulia Palermo (3), Alessandro Porchetta (1), Giuseppe Perugino (2), and Francesco Ricci (1)/titolo:Folding-upon-Repair DNA Nanoswitches for Monitoring the Activity of DNA Repair Enzymes/doi:10.1002%2Fanie.202016223/rivista:Angewandte Chemie (Int. ed., Print)/anno:2021/pagina_da:2/pagina_a:9/intervallo_pagine:2–9/volume:60
ISSN: 1521-3773
1433-7851
Popis: We 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 O(6)-methyl-guanine (O(6)-MeG) nucleobases and labelled with a fluorophore/quencher optical pair. The nanoswitches are rationally designed so that only upon enzymatic demethylation of the O(6)-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.
Databáze: OpenAIRE
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