A Sahakyan, A Mahtey, F Kawasaki, S Balasubramanian
Journal name: 
The alphabet of modified DNA bases goes beyond the conventional four letters, with biological roles being found for many such modifications. Here we describe a novel observation for the thymine base that arises via spontaneous N₁-C₂ ring opening of its oxidation product 5-formyl uracil, after N₃-deprotonation. We first observed this phenomenon in silico though 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 natural existence of Trex in vivo, while screening a number of human cell types and mESC (E14), suggesting potential biological relevance of this modification.
Research group: 
Balasubramanian Group
E-pub date: 
31 Jul 2019
Users with this publication listed: 
Aleksandr Sahakyan
Shankar Balasubramanian