Sumoylation of thymine DNA glycosylase impairs productive binding to substrate sites in DNA.

ABSTRACT: The base excision repair enzyme thymine DNA glycosylase (TDG) protects against mutations by removing thymine or uracil from guanine mispairs and functions in active DNA demethylation by excising 5-formylcytosine (fC) and 5-carboxylcytosine (caC). Post-translational modification of TDG by SUMO (small ubiquitin-like modifier) reduces its glycosylase activity but the mechanism remains unclear. We investigated this problem using biochemical and biophysical approaches and a TDG construct comprising residues 82 to 340 (of 410) that includes the SUMOylation site and the motif for non-covalent SUMO binding. Single turnover kinetics experiments were collected at multiple enzyme concentrations ([E]) and the hyperbolic dependence of activity (k_obs) on [E] yielded the maximal glycosylase ac

SUBMITTER: Pidugu LS 

PROVIDER: S-EPMC11602971 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature