5UZI

Insights into Watson-Crick/Hoogsteen Breathing Dynamics and Damage Repair from the Solution Structure and Dynamic Ensemble of DNA Duplexes containing m1A - A6-DNAm1A16 structure

Summary for 5UZI

• Entry DOI: 10.2210/pdb5uzi/pdb
• Related: 5UZD 5UZF
• NMR Information: BMRB: 30255
• Descriptor: DNA (5'-D(*CP*GP*AP*TP*TP*TP*TP*TP*TP*GP*GP*C)-3'), DNA (5'-D(*GP*CP*CP*(M1A)P*AP*AP*AP*AP*AP*TP*CP*G)-3') (2 entities in total)
• Functional Keywords: hoogsteen base pairs, dna structure and dynamics, n1-methyladenine, damage recognition and repair, nmr structure and dynamic ensembles, dna
• Biological source: synthetic construct; More
• Total number of polymer chains: 2
• Total formula weight: 7338.85

Authors

Sathyamoorthy, B.,Shi, H.,Xue, Y.,Al-Hashimi, H.M. (deposition date: 2017-02-26, release date: 2017-04-05, Last modification date: 2024-05-15)

Primary citation

Sathyamoorthy, B.,Shi, H.,Zhou, H.,Xue, Y.,Rangadurai, A.,Merriman, D.K.,Al-Hashimi, H.M.
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., 45:5586-5601, 2017

PubMed Abstract: 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.

PubMed: 28369571
DOI: 10.1093/nar/gkx186

Experimental method

SOLUTION NMR