Hydroxymethyluracil modifications enhance the flexibility and hydrophilicity of double-stranded DNA

Spencer Carson, James Wilson, Aleksei Aksimentiev, Peter R. Weigele, Meni Wanunu

Research output: Contribution to journalArticlepeer-review


Oxidation of a DNA thymine to 5-hydroxymethyluracil is one of several recently discovered epigenetic modifications. Here, we report the results of nanopore translocation experiments and molecular dynamics simulations that provide insight into the impact of this modification on the structure and dynamics of DNA. When transported through ultrathin solid-state nanopores, short DNA fragments containing thymine modifications were found to exhibit distinct, reproducible features in their transport characteristics that differentiate them from unmodified molecules. Molecular dynamics simulations suggest that 5-hydroxymethyluracil alters the flexibility and hydrophilicity of the DNA molecules, which may account for the differences observed in our nanopore translocation experiments. The altered physico-chemical properties of DNA produced by the thymine modifications may have implications for recognition and processing of such modifications by regulatory DNA-binding proteins.

Original languageEnglish (US)
Pages (from-to)2085-2092
Number of pages8
JournalNucleic acids research
Issue number5
StatePublished - Nov 17 2015

ASJC Scopus subject areas

  • Genetics


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