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TWJ-Screen: an isothermal screening assay to assess ligand/DNA junction interactions in vitro
The quest for chemicals able to operate at selected genomic loci in a spatiotemporally controlled manner is desirable to create manageable DNA damages. Mounting evidence now shows that alternative DNA structures, including G-quadruplexes and branched DNA (or DNA junctions), might hamper proper progr...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5815093/ https://www.ncbi.nlm.nih.gov/pubmed/29149299 http://dx.doi.org/10.1093/nar/gkx1118 |
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author | Guyon, Ludivine Pirrotta, Marc Duskova, Katerina Granzhan, Anton Teulade-Fichou, Marie-Paule Monchaud, David |
author_facet | Guyon, Ludivine Pirrotta, Marc Duskova, Katerina Granzhan, Anton Teulade-Fichou, Marie-Paule Monchaud, David |
author_sort | Guyon, Ludivine |
collection | PubMed |
description | The quest for chemicals able to operate at selected genomic loci in a spatiotemporally controlled manner is desirable to create manageable DNA damages. Mounting evidence now shows that alternative DNA structures, including G-quadruplexes and branched DNA (or DNA junctions), might hamper proper progression of replication fork, thus triggering DNA damages and genomic instability. Therefore, small molecules that stabilize these DNA structures are currently scrutinized as a promising way to create genomic defects that cannot be dealt with properly by cancer cells. While much emphasis has been recently given to G-quadruplexes and related ligands, we report herein on three-way DNA junctions (TWJ) and related ligands. We first highlight the biological implications of TWJ and their strategic relevance as triggers for replicative stress. Then, we describe a new in vitro high-throughput screening assay, TWJ-Screen, which allows for identifying TWJ ligands with both high affinity and selectivity for TWJ over other DNA structures (duplexes and quadruplexes), in a convenient and unbiased manner as demonstrated by the screening of a library of 25 compounds from different chemical families. TWJ-Screen thus represents a reliable mean to uncover molecular tools able to foster replicative stress through an innovative approach, thus providing new strategic opportunities to combat cancers. |
format | Online Article Text |
id | pubmed-5815093 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-58150932018-02-23 TWJ-Screen: an isothermal screening assay to assess ligand/DNA junction interactions in vitro Guyon, Ludivine Pirrotta, Marc Duskova, Katerina Granzhan, Anton Teulade-Fichou, Marie-Paule Monchaud, David Nucleic Acids Res Methods Online The quest for chemicals able to operate at selected genomic loci in a spatiotemporally controlled manner is desirable to create manageable DNA damages. Mounting evidence now shows that alternative DNA structures, including G-quadruplexes and branched DNA (or DNA junctions), might hamper proper progression of replication fork, thus triggering DNA damages and genomic instability. Therefore, small molecules that stabilize these DNA structures are currently scrutinized as a promising way to create genomic defects that cannot be dealt with properly by cancer cells. While much emphasis has been recently given to G-quadruplexes and related ligands, we report herein on three-way DNA junctions (TWJ) and related ligands. We first highlight the biological implications of TWJ and their strategic relevance as triggers for replicative stress. Then, we describe a new in vitro high-throughput screening assay, TWJ-Screen, which allows for identifying TWJ ligands with both high affinity and selectivity for TWJ over other DNA structures (duplexes and quadruplexes), in a convenient and unbiased manner as demonstrated by the screening of a library of 25 compounds from different chemical families. TWJ-Screen thus represents a reliable mean to uncover molecular tools able to foster replicative stress through an innovative approach, thus providing new strategic opportunities to combat cancers. Oxford University Press 2018-02-16 2017-11-15 /pmc/articles/PMC5815093/ /pubmed/29149299 http://dx.doi.org/10.1093/nar/gkx1118 Text en © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Methods Online Guyon, Ludivine Pirrotta, Marc Duskova, Katerina Granzhan, Anton Teulade-Fichou, Marie-Paule Monchaud, David TWJ-Screen: an isothermal screening assay to assess ligand/DNA junction interactions in vitro |
title | TWJ-Screen: an isothermal screening assay to assess ligand/DNA junction interactions in vitro |
title_full | TWJ-Screen: an isothermal screening assay to assess ligand/DNA junction interactions in vitro |
title_fullStr | TWJ-Screen: an isothermal screening assay to assess ligand/DNA junction interactions in vitro |
title_full_unstemmed | TWJ-Screen: an isothermal screening assay to assess ligand/DNA junction interactions in vitro |
title_short | TWJ-Screen: an isothermal screening assay to assess ligand/DNA junction interactions in vitro |
title_sort | twj-screen: an isothermal screening assay to assess ligand/dna junction interactions in vitro |
topic | Methods Online |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5815093/ https://www.ncbi.nlm.nih.gov/pubmed/29149299 http://dx.doi.org/10.1093/nar/gkx1118 |
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