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.