Structural basis of damage recognition by thymine DNA glycosylase: Key roles for N-terminal residues.

ABSTRACT: Thymine DNA Glycosylase (TDG) is a base excision repair enzyme functioning in DNA repair and epigenetic regulation. TDG removes thymine from mutagenic G·T mispairs arising from deamination of 5-methylcytosine (mC), and it processes other deamination-derived lesions including uracil (U). Essential for DNA demethylation, TDG excises 5-formylcytosine and 5-carboxylcytosine, derivatives of mC generated by Tet (ten-eleven translocation) enzymes. Here, we report structural and functional studies of TDG^82-308, a new construct containing 29 more N-terminal residues than TDG^111-308, the construct used for previous structures of DNA-bound TDG. Crystal structures and NMR experiments demonstrate that most of these N-terminal residues are disordered, for substrate- or product-boun

SUBMITTER: Coey CT 

PROVIDER: S-EPMC5137436 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature