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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 m1A.

Publication ,  Journal Article
Sathyamoorthy, B; Shi, H; Zhou, H; Xue, Y; Rangadurai, A; Merriman, DK; Al-Hashimi, HM
Published in: Nucleic Acids Res
May 19, 2017

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 (m1A) lesion affects the structural and dynamic properties of two duplexes. The solution structure and dynamic ensembles of the duplexes reveals that in both cases, m1A forms a m1A•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 m1A recognition and repair.

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Published In

Nucleic Acids Res

DOI

EISSN

1362-4962

Publication Date

May 19, 2017

Volume

45

Issue

9

Start / End Page

5586 / 5601

Location

England

Related Subject Headings

  • Time Factors
  • Thermodynamics
  • Solutions
  • Nucleic Acid Conformation
  • Methylation
  • Magnetic Resonance Spectroscopy
  • Developmental Biology
  • DNA Repair
  • DNA
  • Base Pairing
 

Citation

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Sathyamoorthy, B., Shi, H., Zhou, H., Xue, Y., Rangadurai, A., Merriman, D. K., & Al-Hashimi, H. M. (2017). Insights into Watson-Crick/Hoogsteen breathing dynamics and damage repair from the solution structure and dynamic ensemble of DNA duplexes containing m1A. Nucleic Acids Res, 45(9), 5586–5601. https://doi.org/10.1093/nar/gkx186
Sathyamoorthy, Bharathwaj, Honglue Shi, Huiqing Zhou, Yi Xue, Atul Rangadurai, Dawn K. Merriman, and Hashim M. Al-Hashimi. “Insights into Watson-Crick/Hoogsteen breathing dynamics and damage repair from the solution structure and dynamic ensemble of DNA duplexes containing m1A.Nucleic Acids Res 45, no. 9 (May 19, 2017): 5586–5601. https://doi.org/10.1093/nar/gkx186.
Sathyamoorthy B, Shi H, Zhou H, Xue Y, Rangadurai A, Merriman DK, et al. Insights into Watson-Crick/Hoogsteen breathing dynamics and damage repair from the solution structure and dynamic ensemble of DNA duplexes containing m1A. Nucleic Acids Res. 2017 May 19;45(9):5586–601.
Sathyamoorthy, Bharathwaj, et al. “Insights into Watson-Crick/Hoogsteen breathing dynamics and damage repair from the solution structure and dynamic ensemble of DNA duplexes containing m1A.Nucleic Acids Res, vol. 45, no. 9, May 2017, pp. 5586–601. Pubmed, doi:10.1093/nar/gkx186.
Sathyamoorthy B, Shi H, Zhou H, Xue Y, Rangadurai A, Merriman DK, Al-Hashimi HM. Insights into Watson-Crick/Hoogsteen breathing dynamics and damage repair from the solution structure and dynamic ensemble of DNA duplexes containing m1A. Nucleic Acids Res. 2017 May 19;45(9):5586–5601.
Journal cover image

Published In

Nucleic Acids Res

DOI

EISSN

1362-4962

Publication Date

May 19, 2017

Volume

45

Issue

9

Start / End Page

5586 / 5601

Location

England

Related Subject Headings

  • Time Factors
  • Thermodynamics
  • Solutions
  • Nucleic Acid Conformation
  • Methylation
  • Magnetic Resonance Spectroscopy
  • Developmental Biology
  • DNA Repair
  • DNA
  • Base Pairing