Folding‐upon‐repair DNA nanoswitches for monitoring DNA repair enzymes activity

Nada Farag; Rosanna Mattossovich; Rosa Merlo; Łukasz Nierzwicki; Giulia Palermo; Alessandro Porchetta; Giuseppe Perugino; Francesco Ricci

doi:10.1002/ange.202016223

Folding‐upon‐repair DNA nanoswitches for monitoring DNA repair enzymes activity

Abstract

We demonstrate here 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.

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Authors (8)

Nada Farag
Rosanna Mattossovich
Rosa Merlo
Łukasz Nierzwicki dr inż.
- University of California Riverside
Giulia Palermo dr
Alessandro Porchetta
Giuseppe Perugino
Francesco Ricci dr

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Category:: Articles
Type:: artykuły w czasopismach
Published in:: ANGEWANDTE CHEMIE-INTERNATIONAL EDITION no. 133, pages 7359 - 7365,
ISSN: 1433-7851
Language:: English
Publication year:: 2021
Bibliographic description:: Farag N., Mattossovich R., Merlo R., Nierzwicki Ł., Palermo G., Porchetta A., Perugino G., Ricci F.: Folding‐upon‐repair DNA nanoswitches for monitoring DNA repair enzymes activity// ANGEWANDTE CHEMIE-INTERNATIONAL EDITION -Vol. 133,iss. 13 (2021), s.7359-7365
DOI:: Digital Object Identifier (open in new tab) 10.1002/ange.202016223
Verified by:: Gdańsk University of Technology