DNA Damage Recognition by Bacterial and Human Adenine-DNA Glycosylases: Insights from Non-Canonical Substrates
Year: 2026
Type: article
Abstract: The Escherichia coli adenine-DNA glycosylase (MutY) and its human homologue, MUTYH, protect cells against oxygen-free radical-induced mutagenesis by excising regular adenine impaired with 8-oxo-7,8-dihydro-guanine (8oxoG) in the base excision repair (BER) pathway. However, removal of adenine by MutY and MUTYH from an A·8oxoG pair generated via misincorporation of an oxidized nucleotide during DNA synthesis might induce A·T→C·G transversions. Here, to examine MutY and MUTYH in vitro activities, we used short synthetic DNA duplexes in which the target adenine residue was positioned opposite a variety of DNA base modifications. MUTYH does not excise mismatched adenine in non-canonical DNA substrates, whereas MutY excises adenine mispaired with 1,3-d(GpNpG) cisplatin intra-strand crosslink. In addition, we characterized four MUTYH variants associated with cancer risk, which exhibit the following order of DNA glycosylase deficiency: WT ≥ G169D > G202E ≈ Y165C >> D222N. Human adenine-DNA glycosylase MUTYH and its mutant variants, contrary to bacterial MutY, are not prone to aberrant removal of regular adenine residues opposite modified residues in DNA duplexes. We hypothesize that E. coli MutY is prone to aberrant repair under certain conditions and that this may prevent incorporation of adenine opposite blocking lesions in the template strand.
Source: Biomolecules
DOI: 10.3390/biom16081214
Institutions: Al-Farabi Kazakh National University, Kazakh National Medical University, Centre National de la Recherche Scientifique, Commissariat à l'Énergie Atomique et aux Énergies Alternatives, CEA Grenoble, Institut de Recherche Interdisciplinaire de Grenoble, Systèmes Moléculaires et nanoMatériaux pour l'Énergie et la Santé, New York University, Université Paris-Saclay, Intégrité du génome et cancers, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, University of California, Davis, Novosibirsk State University, Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, L. N. Gumilyov Eurasian National University, Nazarbayev University
Language: English
Topic: DNA Repair Mechanisms
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,258
OpenAlex ID: W7203828260