10.1021/acs.biochem.6b00982.s001 Lakshmi S. Pidugu Lakshmi S. Pidugu Joshua W. Flowers Joshua W. Flowers Christopher T. Coey Christopher T. Coey Edwin Pozharski Edwin Pozharski Marc M. Greenberg Marc M. Greenberg Alexander C. Drohat Alexander C. Drohat Structural Basis for Excision of 5‑Formylcytosine by Thymine DNA Glycosylase American Chemical Society 2016 5- methylcytosine crystal structure site base excision repair enzyme 5- formyldeoxycytidine Structural Basis TET hydrolytically excises fC 5- carboxylcytosine Thymine DNA Glycosylase Thymine DNA glycosylase DNA demethylation TDG 5- formylcytosine 2016-11-02 14:44:33 Journal contribution https://acs.figshare.com/articles/journal_contribution/Structural_Basis_for_Excision_of_5_Formylcytosine_by_Thymine_DNA_Glycosylase/4193577 Thymine DNA glycosylase (TDG) is a base excision repair enzyme with key functions in epigenetic regulation. Performing a critical step in a pathway for active DNA demethylation, TDG removes 5-formylcytosine and 5-carboxylcytosine, oxidized derivatives of 5-methylcytosine that are generated by TET (ten–eleven translocation) enzymes. We determined a crystal structure of TDG bound to DNA with a noncleavable (2′-fluoroarabino) analogue of 5-formyldeoxycytidine flipped into its active site, revealing how it recognizes and hydrolytically excises fC. Together with previous structural and biochemical findings, the results illustrate how TDG employs an adaptable active site to excise a broad variety of nucleobases from DNA.