ArticleNucleic acids research2017
Replication studies of carboxymethylated DNA lesions in human cells.
Article in Nucleic acids research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 19 citations in OpenAlex.
- DamageFormer: a damage-aware multimodal deep learning framework for DNA lesion identification from nanopore sequencing.bioRxiv : the preprint server for biology · 2026Article
- Formation of Carboxymethyl-Phosphotriester Adducts in DNA.Chemical research in toxicology · 2025Article
- Metabolic Activation and DNA Interactions of CarcinogenicInternational journal of molecular sciences · 2022Review
- Polymerases and DNA Repair in Neurons: Implications in Neuronal Survival and Neurodegenerative Diseases.Frontiers in cellular neuroscience · 2022Review
- Detection and Discrimination of DNA Adducts Differing in Size, Regiochemistry, and Functional Group by Nanopore Sequencing.Chemical research in toxicology · 2020Article
- Sequence-Specific Quantitation of Mutagenic DNA Damage via Polymerase Amplification with an Artificial Nucleotide.Journal of the American Chemical Society · 2020Article
- Mammalian DNA Polymerase Kappa Activity and Specificity.Molecules (Basel, Switzerland) · 2019Review
- Biological Evaluation of DNA Biomarkers in a Chemically Defined and Site-Specific Manner.Toxics · 2019Review
- DNA replication studies ofThe Journal of biological chemistry · 2019Article
- Chemical Analysis of DNA Damage.Analytical chemistry · 2018Review
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Metabolic activation of some N-nitroso compounds (NOCs), an important class of DNA damaging agents, can induce the carboxymethylation of nucleobases in DNA. Very little was previously known about how the carboxymethylated DNA lesions perturb DNA replication in human cells. Here, we investigated the effects of five carboxymethylated DNA lesions, i.e. O6-CMdG, N6-CMdA, N4-CMdC, N3-CMdT and O4-CMdT on the efficiency and fidelity of DNA replication in HEK293T human embryonic kidney cells. We found that, while neither N6-CMdA nor N4-CMdC blocked DNA replication or induced mutations, N3-CMdT, O4-CMdT and O6-CMdG moderately blocked DNA replication and induced substantial frequencies of T→A (81%), T→C (68%) and G→A (6.4%) mutations, respectively. In addition, our results revealed that CRISPR-Cas9-mediated depletion of Pol η resulted in significant drops in bypass efficiencies of N4-CMdC and N3-CMdT. Diminution in bypass efficiencies was also observed for N6-CMdA and O6-CMdG upon depletion of Pol κ, and for O6-CMdG upon removal of Pol ζ. Together, our study provided molecular-level insights into the impacts of the carboxymethylated DNA lesions on DNA replication in human cells, revealed the roles of individual translesion synthesis DNA polymerases in bypassing these lesions, and suggested the contributions of O6-CMdG, N3-CMdT and O4-CMdT to the mutations found in p53 gene of human gastrointestinal cancers.
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Registered trials
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