Crystal structures of B-DNA dodecamer containing the epigenetic modifications 5-hydroxymethylcytosine or 5-methylcytosine
| Authors | |
|---|---|
| Year of publication | 2013 |
| Type | Article in Periodical |
| Magazine / Source | Nucleic Acids Research |
| MU Faculty or unit | |
| Citation | |
| Web | http://nar.oxfordjournals.org/content/early/2013/08/20/nar.gkt738.full.pdf+html |
| Doi | http://dx.doi.org/10.1093/nar/gkt738 |
| Field | Biochemistry |
| Keywords | NUCLEIC-ACID STRUCTURES; CIRCULAR-DICHROISM; DEOXYRIBONUCLEIC-ACID; ATOMIC-RESOLUTION; PROTEIN CRYSTALS; BINDING-SITES; MAMMALIAN DNA; CRYSTALLIZATION; PARAMETERS; SOFTWARE |
| Attached files | |
| Description | 5-Hydroxymethylcytosine (5-hmC) was recently identified as a relatively frequent base in eukaryotic genomes. Its physiological function is still unclear, but it is supposed to serve as an intermediate in DNA de novo demethylation. Using X-ray diffraction, we solved five structures of four variants of the d(CGCG AATTCGCG) dodecamer, containing either 5-hmC or 5-methylcytosine (5-mC) at position 3 or at position 9. The observed resolutions were between 1.42 and 1.99A. Cytosine modification in all cases influences neither the whole B-DNA double helix structure nor the modified base pair geometry. The additional hydroxyl group of 5-hmC with rotational freedom along the C5-C5A bond is preferentially oriented in the 30 direction. A comparison of thermodynamic properties of the dodecamers shows no effect of 5- mC modification and a sequence-dependent only slight destabilizing effect of 5-hmC modification. Also taking into account the results of a previous functional study /Munzel et al. (2011)(Improved synthesis and mutagenicity of oligonucleotides containing 5-hydroxymethylcytosine, 5-formylcytosine and 5-carboxylcytosine. Chem. Eur. J., 17, 13782-13788)/, we conclude that the 5 position of cytosine is an ideal place to encode epigenetic information. Like this, neither the helical structure nor the thermodynamics are changed, and polymerases cannot distinguish 5- hmC and 5-mC from unmodified cytosine, all these effects are making the former ones non-mutagenic. |
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