Authors:
RE Hardisty, F Kawasaki, AB Sahakyan, S Balasubramanian
Journal name: 
J Am Chem Soc
Citation info: 
137(29):9270-9272
Abstract: 
We present a chemical method to selectively tag and enrich thymine modifications, 5-formyluracil (5-fU) and 5-hydroxymethyluracil (5-hmU), found naturally in DNA. Inherent reactivity differences have enabled us to tag 5-fU chemoselectively over its C modification counterpart, 5-formylcytosine (5-fC). We rationalized the enhanced reactivity of 5-fU compared to 5-fC via ab initio quantum mechanical calculations. We exploited this chemical tagging reaction to provide proof of concept for the enrichment of 5-fU containing DNA from a pool that contains 5-fC or no modification. We further demonstrate that 5-hmU can be chemically oxidized to 5-fU, providing a strategy for the enrichment of 5-hmU. These methods will enable the mapping of 5-fU and 5-hmU in genomic DNA, to provide insights into their functional role and dynamics in biology.
DOI: 
http://doi.org/10.1021/jacs.5b03730
Research group: 
Balasubramanian Group
E-pub date: 
29 Jul 2015