ArticleGenes and environment : the official journal of the Japanese Environmental Mutagen Society2016
Mutagenic consequences of cytosine alterations site-specifically embedded in the human genome.
Article in Genes and environment : the official journal of the Japanese Environmental Mutagen Society, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 33 citations in OpenAlex.
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- DNA Glycosylases Define the Outcome of Endogenous Base Modifications.International journal of molecular sciences · 2023Review
- Metabolomics Analysis as a Tool to Measure Cobalt Neurotoxicity: An In Vitro Validation.Metabolites · 2023Article
- Single-strand mismatch and damage patterns revealed by single-molecule DNA sequencing.bioRxiv : the preprint server for biology · 2023Article
- Analyses of mutational patterns induced by formaldehyde and acetaldehyde reveal similarity to a common mutational signature.G3 (Bethesda, Md.) · 2022Article
- Intrinsic base substitution patterns in diverse species reveal links to cancer and metabolism.Genetics · 2022Article
- Phenotypic and mutational spectrum of ROR2-related Robinow syndrome.Human mutation · 2022Article
- Gene expression levels modulate germline mutation rates through the compound effects of transcription-coupled repair and damage.Human genetics · 2022Article
- DNA Methylation and Detoxification in the EarthwormToxics · 2022Article
- De Novo Mutation Rate Variation and Its Determinants in Chlamydomonas.Molecular biology and evolution · 2021Article
- DNA damage in cancer development: special implications in viral oncogenesis.American journal of cancer research · 2021Article
- Making it or breaking it: DNA methylation and genome integrity.Essays in biochemistry · 2020Review
- Focus on UV-Induced DNA Damage and Repair-Disease Relevance and Protective Strategies.International journal of molecular sciences · 2020Review
- Mutational processes of distinct POLE exonuclease domain mutants drive an enrichment of a specific TP53 mutation in colorectal cancer.PLoS genetics · 2020Article
- Epigenetic signatures in cardiac fibrosis, special emphasis on DNA methylation and histone modification.Heart failure reviews · 2018Review
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionCytosine residues in CpG dinucleotides often undergo various types of modification, such as methylation, deamination, and halogenation. These types of modifications can be pro-mutagenic and can contribute to the formation of mutational hotspots in cells. To analyze mutations induced by DNA modifications in the human genome, we recently developed a system for tracing DNA adducts in targeted mutagenesis (TATAM). In this system, a modified/damaged base is site-specifically introduced into intron 4 of thymidine kinase genes in human lymphoblastoid cells. To further the understanding of the mutagenesis of cytosine modification, we directly introduced different types of altered cytosine residues into the genome and investigated their genomic consequences using the TATAM system.
findingsIn the genome, the pairing of thymine and 5-bromouracil with guanine, resulting from the deamination of 5-methylcytosine and 5-bromocytosine, respectively, was highly pro-mutagenic compared with the pairing of uracil with guanine, resulting from the deamination of cytosine residues.
conclusionsThe deamination of 5-methylcytosine and 5-bromocytosine rather than that of normal cytosine dramatically enhances the mutagenic potential in the human genome.
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