Lin, Shan-Meng;
Huang, Hsiang-Ti;
Fang, Pei-Ju;
Chang, Chi-Fon;
Satange, Roshan;
Chang, Chung-ke;
Chou, Shan-Ho;
... Hou, Ming-Hon; + view all
(2024)
Structural basis of water-mediated cis Watson–Crick/Hoogsteen base-pair formation in non-CpG methylation.
Nucleic Acids Research
, 52
(14)
pp. 8566-8579.
10.1093/nar/gkae594.
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Structural basis of water-mediated cis Watson-CrickHoogsteen base-pair formation in non-CpG methylation.pdf - Published Version Download (2MB) | Preview |
Abstract
Non-CpG methylation is associated with several cellular processes, especially neuronal development and cancer, while its effect on DNA structure remains unclear. We have determined the crystal structures of DNA duplexes containing -CGCCG- regions as CCG repeat motifs that comprise a non-CpG site with or without cytosine methylation. Crystal structure analyses have revealed that the mC:G base-pair can simultaneously form two alternative conformations arising from non-CpG methylation, including a unique water-mediated cis Watson–Crick/Hoogsteen, (w)cWH, and Watson–Crick (WC) geometries, with partial occupancies of 0.1 and 0.9, respectively. NMR studies showed that an alternative conformation of methylated mC:G base-pair at non-CpG step exhibits characteristics of cWH with a syn-guanosine conformation in solution. DNA duplexes complexed with the DNA binding drug echinomycin result in increased occupancy of the (w)cWH geometry in the methylated base-pair (from 0.1 to 0.3). Our structural results demonstrated that cytosine methylation at a non-CpG step leads to an anti→syntransition of its complementary guanosine residue toward the (w)cWH geometry as a partial population of WC, in both drug-bound and naked mC:G base pairs. This particular geometry is specific to non-CpG methylated dinucleotide sites in B-form DNA. Overall, the current study provides new insights into DNA conformation during epigenetic regulation.
| Type: | Article |
|---|---|
| Title: | Structural basis of water-mediated cis Watson–Crick/Hoogsteen base-pair formation in non-CpG methylation |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1093/nar/gkae594 |
| Publisher version: | http://dx.doi.org/10.1093/nar/gkae594 |
| Language: | English |
| Additional information: | Copyright © The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10197683 |
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