bi6b00982_si_001.pdf (3.14 MB)
Structural Basis for Excision of 5‑Formylcytosine by Thymine DNA Glycosylase
journal contribution
posted on 2016-11-02, 14:44 authored by Lakshmi
S. Pidugu, Joshua W. Flowers, Christopher T. Coey, Edwin Pozharski, Marc M. Greenberg, Alexander C. DrohatThymine 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.