A Spontaneous Ring-Opening Reaction Leads to a Repair-Resistant Thymine Oxidation Product in Genomic DNA

Chembiochem. 2020 Feb 3;21(3):320-323. doi: 10.1002/cbic.201900484. Epub 2019 Oct 23.


The alphabet of modified DNA bases goes beyond the conventional four letters, with biological roles being found for many such modifications. Herein, we describe the observation of a modified thymine base that arises from spontaneous N1 -C2 ring opening of the oxidation product 5-formyl uracil, after N3 deprotonation. We first observed this phenomenon in silico through ab initio calculations, followed by in vitro experiments to verify its formation at a mononucleoside level and in a synthetic DNA oligonucleotide context. We show that the new base modification (Trex , thymine ring expunged) can form under physiological conditions, and is resistant to the action of common repair machineries. Furthermore, we found cases of the natural existence of Trex while screening a number of human cell types and mESC (E14), thus suggesting potential biological relevance of this modification.

Keywords: base modification; nucleic acids; oxidative damage; repair resistance; ring opening; thymine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • DNA / genetics
  • DNA / metabolism*
  • HeLa Cells
  • Humans
  • Molecular Structure
  • Oxidation-Reduction
  • Thymine / chemistry
  • Thymine / metabolism*


  • DNA
  • Thymine