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Insights into Watson–Crick/Hoogsteen breathing dynamics and damage repair from the solution structure and dynamic ensemble of DNA duplexes containing m(1)A

In the canonical DNA double helix, Watson–Crick (WC) base pairs (bps) exist in dynamic equilibrium with sparsely populated (∼0.02–0.4%) and short-lived (lifetimes ∼0.2–2.5 ms) Hoogsteen (HG) bps. To gain insights into transient HG bps, we used solution-state nuclear magnetic resonance spectroscopy,...

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Autores principales: Sathyamoorthy, Bharathwaj, Shi, Honglue, Zhou, Huiqing, Xue, Yi, Rangadurai, Atul, Merriman, Dawn K., Al-Hashimi, Hashim M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5435913/
https://www.ncbi.nlm.nih.gov/pubmed/28369571
http://dx.doi.org/10.1093/nar/gkx186
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author Sathyamoorthy, Bharathwaj
Shi, Honglue
Zhou, Huiqing
Xue, Yi
Rangadurai, Atul
Merriman, Dawn K.
Al-Hashimi, Hashim M.
author_facet Sathyamoorthy, Bharathwaj
Shi, Honglue
Zhou, Huiqing
Xue, Yi
Rangadurai, Atul
Merriman, Dawn K.
Al-Hashimi, Hashim M.
author_sort Sathyamoorthy, Bharathwaj
collection PubMed
description In the canonical DNA double helix, Watson–Crick (WC) base pairs (bps) exist in dynamic equilibrium with sparsely populated (∼0.02–0.4%) and short-lived (lifetimes ∼0.2–2.5 ms) Hoogsteen (HG) bps. To gain insights into transient HG bps, we used solution-state nuclear magnetic resonance spectroscopy, including measurements of residual dipolar couplings and molecular dynamics simulations, to examine how a single HG bp trapped using the N1-methylated adenine (m(1)A) lesion affects the structural and dynamic properties of two duplexes. The solution structure and dynamic ensembles of the duplexes reveals that in both cases, m(1)A forms a m(1)A•T HG bp, which is accompanied by local and global structural and dynamic perturbations in the double helix. These include a bias toward the BI backbone conformation; sugar repuckering, major-groove directed kinking (∼9°); and local melting of neighboring WC bps. These results provide atomic insights into WC/HG breathing dynamics in unmodified DNA duplexes as well as identify structural and dynamic signatures that could play roles in m(1)A recognition and repair.
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spelling pubmed-54359132017-05-22 Insights into Watson–Crick/Hoogsteen breathing dynamics and damage repair from the solution structure and dynamic ensemble of DNA duplexes containing m(1)A Sathyamoorthy, Bharathwaj Shi, Honglue Zhou, Huiqing Xue, Yi Rangadurai, Atul Merriman, Dawn K. Al-Hashimi, Hashim M. Nucleic Acids Res Structural Biology In the canonical DNA double helix, Watson–Crick (WC) base pairs (bps) exist in dynamic equilibrium with sparsely populated (∼0.02–0.4%) and short-lived (lifetimes ∼0.2–2.5 ms) Hoogsteen (HG) bps. To gain insights into transient HG bps, we used solution-state nuclear magnetic resonance spectroscopy, including measurements of residual dipolar couplings and molecular dynamics simulations, to examine how a single HG bp trapped using the N1-methylated adenine (m(1)A) lesion affects the structural and dynamic properties of two duplexes. The solution structure and dynamic ensembles of the duplexes reveals that in both cases, m(1)A forms a m(1)A•T HG bp, which is accompanied by local and global structural and dynamic perturbations in the double helix. These include a bias toward the BI backbone conformation; sugar repuckering, major-groove directed kinking (∼9°); and local melting of neighboring WC bps. These results provide atomic insights into WC/HG breathing dynamics in unmodified DNA duplexes as well as identify structural and dynamic signatures that could play roles in m(1)A recognition and repair. Oxford University Press 2017-05-19 2017-03-21 /pmc/articles/PMC5435913/ /pubmed/28369571 http://dx.doi.org/10.1093/nar/gkx186 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 Structural Biology
Sathyamoorthy, Bharathwaj
Shi, Honglue
Zhou, Huiqing
Xue, Yi
Rangadurai, Atul
Merriman, Dawn K.
Al-Hashimi, Hashim M.
Insights into Watson–Crick/Hoogsteen breathing dynamics and damage repair from the solution structure and dynamic ensemble of DNA duplexes containing m(1)A
title Insights into Watson–Crick/Hoogsteen breathing dynamics and damage repair from the solution structure and dynamic ensemble of DNA duplexes containing m(1)A
title_full Insights into Watson–Crick/Hoogsteen breathing dynamics and damage repair from the solution structure and dynamic ensemble of DNA duplexes containing m(1)A
title_fullStr Insights into Watson–Crick/Hoogsteen breathing dynamics and damage repair from the solution structure and dynamic ensemble of DNA duplexes containing m(1)A
title_full_unstemmed Insights into Watson–Crick/Hoogsteen breathing dynamics and damage repair from the solution structure and dynamic ensemble of DNA duplexes containing m(1)A
title_short Insights into Watson–Crick/Hoogsteen breathing dynamics and damage repair from the solution structure and dynamic ensemble of DNA duplexes containing m(1)A
title_sort insights into watson–crick/hoogsteen breathing dynamics and damage repair from the solution structure and dynamic ensemble of dna duplexes containing m(1)a
topic Structural Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5435913/
https://www.ncbi.nlm.nih.gov/pubmed/28369571
http://dx.doi.org/10.1093/nar/gkx186
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