Characterizing the excision of 7,8-dihydro-8-oxoadenine by thymine DNA glycosylase.

ABSTRACT: Oxidation of DNA yields mutagenic and cytotoxic lesions that threaten genomic integrity, cause cancer and other diseases, and contribute to aging. Oxidative damage is countered by base excision repair, a pathway initiated by DNA glycosylases, which cleave bases through N-glycosyl bond hydrolysis. The major adenine oxidative lesion, 7,8-dihydro-8-oxoadenine (oxoA), is mutagenic in mammalian cells, but repair mechanisms are poorly understood. Thymine DNA glycosylase (TDG) removes T from mutagenic G⋅T mispairs arising through 5-methylcytosine deamination and mediates active DNA demethylation by excising 5-formylcytosine and 5-carboxylcytosine (caC). TDG excises oxoA from G⋅oxoA, A⋅oxoA, or C⋅oxoA pairs with remarkably high activity and from T⋅oxoA pairs with lower activity, comparable to that

SUBMITTER: Servius HW 

PROVIDER: S-EPMC12272883 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature