ArticleNucleic acids research2020
Mutation signatures specific to DNA alkylating agents in yeast and cancers.
Article in Nucleic acids research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 44 citations in OpenAlex.
- Motif-centered analyses reveal universal and tissue-specific mutagenic mechanisms operating in the human body.NAR cancer · 2026Article
- Break-induced replication forms long mutable single-strand DNA during meiosis.Nature communications · 2026Article
- Redox stress agents strongly enhance mutagenesis during horizontal gene transfer in bacteria and leave distinct mutational and metabolic footprints.bioRxiv : the preprint server for biology · 2026Article
- APOBEC3A is the predominant global editor of cytosines in human mRNAs and in single-strand RNA viruses.G3 (Bethesda, Md.) · 2026Article
- Motif-Centered Analyses Reveal Universal and Tissue-Specific Mutagenic Mechanisms Operating in the Human Body.bioRxiv : the preprint server for biology · 2026Article
- Comparative whole-genome analyses of articular chondrocytes and skin fibroblasts reveal distinct genome instability landscapes in mesenchymal cell types.PLoS genetics · 2026Article
- Increased replication-associated single-stranded DNA promotes formaldehyde-induced mutagenesis.bioRxiv : the preprint server for biology · 2026Article
- IARC Group 1 Pharmaceuticals and Associated Cancer Risks: A Nationwide Population-Based Cohort Study in Korea.Cancer research and treatment · 2026Article
- Comparative whole-genome analyses of articular chondrocytes and skin fibroblasts reveal distinct genome instability landscapes in mesenchymal cell types.bioRxiv : the preprint server for biology · 2026Article
- APOBEC3A is the predominant global editor of cytosines in human mRNAs and in single-strand RNA viruses.bioRxiv : the preprint server for biology · 2026Article
- Nucleotide salvage, genome instability, and potential therapeutic applications.Nucleic acids research · 2026Review
- Translesion polymerases and DNA-protein crosslink repair shapes the cellular response to formaldehyde-induced DNA damage in ssDNA.Nucleic acids research · 2025Article
- Methylglyoxal mutagenizes single-stranded DNA via Rev1-associated slippage and mispairing.Nucleic acids research · 2025Article
- Methylglyoxal mutagenizes single-stranded DNA via Rev1-associated slippage and mispairing.bioRxiv : the preprint server for biology · 2025Article
- Direct Measurement of 8OG Syn-Anti Flips in Mutagenic 8OG·A and Long-Range Damage-Dependent Hoogsteen Breathing Dynamics UsingThe journal of physical chemistry. B · 2024Article
- Direct Measurement of 8OGbioRxiv : the preprint server for biology · 2024Article
- Glycidamide-induced hypermutation in yeast single-stranded DNA reveals a ubiquitous clock-like mutational motif in humans.Nucleic acids research · 2023Article
- Changes in metabolic landscapes shape divergent but distinct mutational signatures and cytotoxic consequences of redox stress.Nucleic acids research · 2023Article
- The interplay between noncoding RNAs and drug resistance in hepatocellular carcinoma: the big impact of little things.Journal of translational medicine · 2023Review
- Identification of Some Glutamic Acid Derivatives with Biological Potential by Computational Methods.Molecules (Basel, Switzerland) · 2023Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Alkylation is one of the most ubiquitous forms of DNA lesions. However, the motif preferences and substrates for the activity of the major types of alkylating agents defined by their nucleophilic substitution reactions (SN1 and SN2) are still unclear. Utilizing yeast strains engineered for large-scale production of single-stranded DNA (ssDNA), we probed the substrate specificity, mutation spectra and signatures associated with DNA alkylating agents. We determined that SN1-type agents preferably mutagenize double-stranded DNA (dsDNA), and the mutation signature characteristic of the activity of SN1-type agents was conserved across yeast, mice and human cancers. Conversely, SN2-type agents preferably mutagenize ssDNA in yeast. Moreover, the spectra and signatures derived from yeast were detectable in lung cancers, head and neck cancers and tumors from patients exposed to SN2-type alkylating chemicals. The estimates of mutation loads associated with the SN2-type alkylation signature were higher in lung tumors from smokers than never-smokers, pointing toward the mutagenic activity of the SN2-type alkylating carcinogens in cigarettes. In summary, our analysis of mutations in yeast strains treated with alkylating agents, as well as in whole-exome and whole-genome-sequenced tumors identified signatures highly specific to alkylation mutagenesis and indicate the pervasive nature of alkylation-induced mutagenesis in cancers.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.