6alt | pdb_00006alt

Solution structure of a DNA dodecamer with 5-methylcytosine at the 3rd and 9th position

spinqualitylabelsall models 6alt, 11 NMR models Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6alt is a 2 chain structure. This structure supersedes the now removed PDB entry 5tmi. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. NonStd Res: 5CM, DCZ Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed DNA damage can affect various regulatory elements of the genome, with the consequences for DNA structure, dynamics, and interaction with proteins remaining largely unexplored. We used solution NMR spectroscopy, restrained and free molecular dynamics to obtain the structures and investigate dominant motions for a set of DNA duplexes containing CpG sites permuted with combinations of 5-methylcytosine (mC), the primary epigenetic base, and 8-oxoguanine (oxoG), an abundant DNA lesion. Guanine oxidation significantly changed the motion in both hemimethylated and fully methylated DNA, increased base pair breathing, induced BI-->BII transition in the backbone 3' to the oxoG and reduced the variability of shift and tilt helical parameters. UV melting experiments corroborated the NMR and molecular dynamics results, showing significant destabilization of all methylated contexts by oxoG. Notably, some dynamic and thermodynamic effects were not additive in the fully methylated oxidized CpG, indicating that the introduced modifications interact with each other. Finally, we show that the presence of oxoG biases the recognition of methylated CpG dinucleotides by ROS1, a plant enzyme involved in epigenetic DNA demethylation, in favor of the oxidized DNA strand. Thus, the conformational and dynamic effects of spurious DNA oxidation in the regulatory CpG dinucleotide can have far-reaching biological consequences. Oxidative damage to epigenetically methylated sites affects DNA stability, dynamics and enzymatic demethylation.,Gruber DR, Toner JJ, Miears HL, Shernyukov AV, Kiryutin AS, Lomzov AA, Endutkin AV, Grin IR, Petrova DV, Kupryushkin MS, Yurkovskaya AV, Johnson EC, Okon M, Bagryanskaya EG, Zharkov DO, Smirnov SL Nucleic Acids Res. 2018 Nov 16;46(20):10827-10839. doi: 10.1093/nar/gky893. PMID:30289469 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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