Details

Autor(en) / Beteiligte

• Sathyamoorthy, Bharathwaj
• Shi, Honglue
• Zhou, Huiqing
• Xue, Yi
• Rangadurai, Atul
• Merriman, Dawn K
• Al-Hashimi, Hashim M

Titel

Insights into Watson-Crick/Hoogsteen breathing dynamics and damage repair from the solution structure and dynamic ensemble of DNA duplexes containing m1A

Ist Teil von

• Nucleic acids research, 2017-05, Vol.45 (9), p.5586-5601

Ort / Verlag

England

Erscheinungsjahr

2017

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.