title: Hydroxymethyluracil modifications enhance the flexibility and hydrophilicity of double-stranded DNA.
abstract: 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.
authors.affiliation: Department of Physics, Northeastern University, Boston, MA, USA.
authors.forename: Spencer
authors.initials: S
authors.lastname: Carson
authors.affiliation: Department of Physics, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
authors.forename: James
authors.initials: J
authors.lastname: Wilson
authors.affiliation: Department of Physics, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
authors.forename: Aleksei
authors.initials: A
authors.lastname: Aksimentiev
authors.affiliation: New England Biolabs, Ipswich, MA, USA weigele@neb.com.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Weigele
authors.affiliation: Department of Physics, Northeastern University, Boston, MA, USA Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA, USA wanunu@neu.edu.
authors.forename: Meni
authors.initials: M
authors.lastname: Wanunu
mesh_terms: D004247:DNA / Q000737:chemistry*; D004268:DNA-Binding Proteins / Q000737:chemistry; D044127:Epigenesis, Genetic; D057927:Hydrophobic and Hydrophilic Interactions; D056004:Molecular Dynamics Simulation; D058608:Nanopores; D009691:Nucleic Acid Denaturation; D010084:Oxidation-Reduction; D010432:Pentoxyl / Q000031:analogs & derivatives* / Q000737:chemistry; D011485:Protein Binding; D013499:Surface Properties; D013941:Thymine / Q000737:chemistry*
chemical_list: D004268:DNA-Binding Proteins; C008055:5-hydroxymethyluracil; D010432:Pentoxyl; D004247:DNA; D013941:Thymine