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Publication Abstract from PubMed

In the canonical DNA double helix, Watson-Crick (WC) base pairs (bps) exist in dynamic equilibrium with sparsely populated ( approximately 0.02-0.4%) and short-lived (lifetimes approximately 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 ( approximately 9 degrees ); 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.

Insights into Watson-Crick/Hoogsteen breathing dynamics and damage repair from the solution structure and dynamic ensemble of DNA duplexes containing m1A.,Sathyamoorthy B, Shi H, Zhou H, Xue Y, Rangadurai A, Merriman DK, Al-Hashimi HM Nucleic Acids Res. 2017 Mar 21. doi: 10.1093/nar/gkx186. PMID:28369571^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.