4GLH

DNA dodecamer containing 5-hydroxymethyl cytosine

Summary for 4GLH

• Entry DOI: 10.2210/pdb4glh/pdb
• Descriptor: DNA (5'-D(*CP*GP*CP*GP*AP*AP*TP*TP*(5HC)P*GP*CP*G)-3'), POTASSIUM ION (3 entities in total)
• Functional Keywords: b-dna dodecamer, epigenetics, 5-hydroxymethyl cytosine, dna
• Biological source: Synthetic construct
• Total number of polymer chains: 2
• Total formula weight: 7465.03

Authors

Spingler, B.,Renciuk, D.,Vorlickova, M. (deposition date: 2012-08-14, release date: 2013-08-28, Last modification date: 2023-09-13)

Primary citation

Renciuk, D.,Blacque, O.,Vorlickova, M.,Spingler, B.
Crystal structures of B-DNA dodecamer containing the epigenetic modifications 5-hydroxymethylcytosine or 5-methylcytosine.
Nucleic Acids Res., 41:9891-9900, 2013

PubMed Abstract: 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(CGCGAATTCGCG) 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 1.99 Å. 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 3' 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 [Münzel 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.

PubMed: 23963698
DOI: 10.1093/nar/gkt738

Experimental method

X-RAY DIFFRACTION (1.662 Å)