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Revealing structural peculiarities of homopurine GA repetition stuck by i-motif clip
Non-canonical forms of nucleic acids represent challenging objects for both structure-determination and investigation of their potential role in living systems. In this work, we uncover a structure adopted by GA repetition locked in a parallel homoduplex by an i-motif. A series of DNA oligonucleotid...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8599794/ https://www.ncbi.nlm.nih.gov/pubmed/34718718 http://dx.doi.org/10.1093/nar/gkab915 |
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author | Novotný, Aleš Novotný, Jan Kejnovská, Iva Vorlíčková, Michaela Fiala, Radovan Marek, Radek |
author_facet | Novotný, Aleš Novotný, Jan Kejnovská, Iva Vorlíčková, Michaela Fiala, Radovan Marek, Radek |
author_sort | Novotný, Aleš |
collection | PubMed |
description | Non-canonical forms of nucleic acids represent challenging objects for both structure-determination and investigation of their potential role in living systems. In this work, we uncover a structure adopted by GA repetition locked in a parallel homoduplex by an i-motif. A series of DNA oligonucleotides comprising GAGA segment and C(3) clip is analyzed by NMR and CD spectroscopies to understand the sequence–structure–stability relationships. We demonstrate how the relative position of the homopurine GAGA segment and the C(3) clip as well as single-base mutations (guanine deamination and cytosine methylation) affect base pairing arrangement of purines, i-motif topology and overall stability. We focus on oligonucleotides C(3)GAGA and methylated GAGAC(3) exhibiting the highest stability and structural uniformity which allowed determination of high-resolution structures further analyzed by unbiased molecular dynamics simulation. We describe sequence-specific supramolecular interactions on the junction between homoduplex and i-motif blocks that contribute to the overall stability of the structures. The results show that the distinct structural motifs can not only coexist in the tight neighborhood within the same molecule but even mutually support their formation. Our findings are expected to have general validity and could serve as guides in future structure and stability investigations of nucleic acids. |
format | Online Article Text |
id | pubmed-8599794 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-85997942021-11-18 Revealing structural peculiarities of homopurine GA repetition stuck by i-motif clip Novotný, Aleš Novotný, Jan Kejnovská, Iva Vorlíčková, Michaela Fiala, Radovan Marek, Radek Nucleic Acids Res Chemical Biology and Nucleic Acid Chemistry Non-canonical forms of nucleic acids represent challenging objects for both structure-determination and investigation of their potential role in living systems. In this work, we uncover a structure adopted by GA repetition locked in a parallel homoduplex by an i-motif. A series of DNA oligonucleotides comprising GAGA segment and C(3) clip is analyzed by NMR and CD spectroscopies to understand the sequence–structure–stability relationships. We demonstrate how the relative position of the homopurine GAGA segment and the C(3) clip as well as single-base mutations (guanine deamination and cytosine methylation) affect base pairing arrangement of purines, i-motif topology and overall stability. We focus on oligonucleotides C(3)GAGA and methylated GAGAC(3) exhibiting the highest stability and structural uniformity which allowed determination of high-resolution structures further analyzed by unbiased molecular dynamics simulation. We describe sequence-specific supramolecular interactions on the junction between homoduplex and i-motif blocks that contribute to the overall stability of the structures. The results show that the distinct structural motifs can not only coexist in the tight neighborhood within the same molecule but even mutually support their formation. Our findings are expected to have general validity and could serve as guides in future structure and stability investigations of nucleic acids. Oxford University Press 2021-10-28 /pmc/articles/PMC8599794/ /pubmed/34718718 http://dx.doi.org/10.1093/nar/gkab915 Text en © The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Chemical Biology and Nucleic Acid Chemistry Novotný, Aleš Novotný, Jan Kejnovská, Iva Vorlíčková, Michaela Fiala, Radovan Marek, Radek Revealing structural peculiarities of homopurine GA repetition stuck by i-motif clip |
title | Revealing structural peculiarities of homopurine GA repetition stuck by i-motif clip |
title_full | Revealing structural peculiarities of homopurine GA repetition stuck by i-motif clip |
title_fullStr | Revealing structural peculiarities of homopurine GA repetition stuck by i-motif clip |
title_full_unstemmed | Revealing structural peculiarities of homopurine GA repetition stuck by i-motif clip |
title_short | Revealing structural peculiarities of homopurine GA repetition stuck by i-motif clip |
title_sort | revealing structural peculiarities of homopurine ga repetition stuck by i-motif clip |
topic | Chemical Biology and Nucleic Acid Chemistry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8599794/ https://www.ncbi.nlm.nih.gov/pubmed/34718718 http://dx.doi.org/10.1093/nar/gkab915 |
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