Insights into Watson-Crick/Hoogsteen breathing dynamics and damage repair from the solution structure and dynamic ensemble of DNA duplexes containing m1A.
| dc.contributor.author | Sathyamoorthy, Bharathwaj | |
| dc.contributor.author | Shi, Honglue | |
| dc.contributor.author | Zhou, Huiqing | |
| dc.contributor.author | Xue, Yi | |
| dc.contributor.author | Rangadurai, Atul | |
| dc.contributor.author | Merriman, Dawn K | |
| dc.contributor.author | Al-Hashimi, Hashim M | |
| dc.date.accessioned | 2018-09-18T02:59:32Z | |
| dc.date.available | 2018-09-18T02:59:32Z | |
| dc.date.issued | 2017-05 | |
| dc.date.updated | 2018-09-18T02:59:27Z | |
| dc.description.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. | |
| dc.identifier | 3076971 | |
| dc.identifier.issn | 0305-1048 | |
| dc.identifier.issn | 1362-4962 | |
| dc.identifier.uri | ||
| dc.language | eng | |
| dc.publisher | Oxford University Press (OUP) | |
| dc.relation.ispartof | Nucleic acids research | |
| dc.relation.isversionof | 10.1093/nar/gkx186 | |
| dc.subject | Adenine | |
| dc.subject | DNA | |
| dc.subject | Solutions | |
| dc.subject | Magnetic Resonance Spectroscopy | |
| dc.subject | DNA Repair | |
| dc.subject | Nucleic Acid Conformation | |
| dc.subject | Base Pairing | |
| dc.subject | Methylation | |
| dc.subject | Thermodynamics | |
| dc.subject | Time Factors | |
| dc.title | Insights into Watson-Crick/Hoogsteen breathing dynamics and damage repair from the solution structure and dynamic ensemble of DNA duplexes containing m1A. | |
| dc.type | Journal article | |
| pubs.begin-page | 5586 | |
| pubs.end-page | 5601 | |
| pubs.issue | 9 | |
| pubs.organisational-group | School of Medicine | |
| pubs.organisational-group | Duke | |
| pubs.organisational-group | Biochemistry | |
| pubs.organisational-group | Basic Science Departments | |
| pubs.organisational-group | Student | |
| pubs.organisational-group | Chemistry | |
| pubs.organisational-group | Trinity College of Arts & Sciences | |
| pubs.publication-status | Published | |
| pubs.volume | 45 |
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