ArticleNucleic acids research2012
Biochemical and structural characterization of the glycosylase domain of MBD4 bound to thymine and 5-hydroxymethyuracil-containing DNA.
Article in Nucleic acids research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 84 citations in OpenAlex.
- Human PMS1-dependent non-canonical mismatch repair engages with MBD4 to repair methylated CpG deamination.Nucleic acids research · 2026Article
- Mapping DNA glycosylase binding across lesion sequence contexts reveals extended sequence and structural recognition logic.Nature communications · 2026Article
- Genetic Variations in the M6A Modification Pathway as Potential Predictors of Imatinib Secondary Resistance in Gastrointestinal Stromal Tumors.Journal of clinical medicine · 2026Article
- A founder heterozygous mutation in methyl-CpG binding domain protein 4 (MBD4) prevalent among Israeli Christian Arabs predisposes to increased mutagenesis.Haematologica · 2026Article
- 8-Oxoguanine: A Lesion, an Epigenetic Mark, or a Molecular Signal?International journal of molecular sciences · 2025Review
- Structure of a DNA Glycosylase Bound to a Nicked T:G Mismatch-Containing DNA.Molecules (Basel, Switzerland) · 2025Article
- Article
- Repair and DNA Polymerase Bypass of Clickable Pyrimidine Nucleotides.Biomolecules · 2024Article
- Probing the Conformational Restraints of DNA Damage Recognition with β-L-Nucleotides.International journal of molecular sciences · 2024Article
- Enhanced thermal stability enables human mismatch-specific thymine-DNA glycosylase to catalyse futile DNA repair.PloS one · 2024Article
- Glycidamide-induced hypermutation in yeast single-stranded DNA reveals a ubiquitous clock-like mutational motif in humans.Nucleic acids research · 2023Article
- Gene editing with 'pencil' rather than 'scissors' in human pluripotent stem cells.Stem cell research & therapy · 2023Review
- Recognition of a Clickable Abasic Site Analog by DNA Polymerases and DNA Repair Enzymes.International journal of molecular sciences · 2022Article
- Kinetics and thermodynamics of BI-BII interconversion altered by T:G mismatches in DNA.Biophysical journal · 2022Article
- High expression of uracil DNA glycosylase determines C to T substitution in human pluripotent stem cells.Molecular therapy. Nucleic acids · 2022Article
- Chemical and enzymatic modifications of 5-methylcytosine at the intersection of DNA damage, repair, and epigenetic reprogramming.PloS one · 2022Article
- Review
- Deficiency of replication-independent DNA mismatch repair drives a 5-methylcytosine deamination mutational signature in cancer.Science advances · 2021Article
- Structural Insights into the Mechanism of Base Excision by MBD4.Journal of molecular biology · 2021Article
- Insights into the substrate discrimination mechanisms of methyl-CpG-binding domain 4.The Biochemical journal · 2021Article
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Active DNA demethylation in mammals occurs via hydroxylation of 5-methylcytosine to 5-hydroxymethylcytosine (5hmC) by the ten-eleven translocation family of proteins (TETs). 5hmC residues in DNA can be further oxidized by TETs to 5-carboxylcytosines and/or deaminated by the Activation Induced Deaminase/Apolipoprotein B mRNA-editing enzyme complex family proteins to 5-hydromethyluracil (5hmU). Excision and replacement of these intermediates is initiated by DNA glycosylases such as thymine-DNA glycosylase (TDG), methyl-binding domain protein 4 (MBD4) and single-strand specific monofunctional uracil-DNA glycosylase 1 in the base excision repair pathway. Here, we report detailed biochemical and structural characterization of human MBD4 which contains mismatch-specific TDG activity. Full-length as well as catalytic domain (residues 426-580) of human MBD4 (MBD4(cat)) can remove 5hmU when opposite to G with good efficiency. Here, we also report six crystal structures of human MBD4(cat): an unliganded form and five binary complexes with duplex DNA containing a T•G, 5hmU•G or AP•G (apurinic/apyrimidinic) mismatch at the target base pair. These structures reveal that MBD4(cat) uses a base flipping mechanism to specifically recognize thymine and 5hmU. The recognition mechanism of flipped-out 5hmU bases in MBD4(cat) active site supports the potential role of MBD4, together with TDG, in maintenance of genome stability and active DNA demethylation in mammals.
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