ArticleOncogene2012
5-aza-2'-deoxycytidine-induced genome rearrangements are mediated by DNMT1.
Article in Oncogene, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 70 citations in OpenAlex.
- Epigenetic regulation of major histocompatibility complexes in gastrointestinal malignancies and the potential for clinical interception.Clinical epigenetics · 2024Pooled it
- p53 status determines the epigenetic response to demethylating agents azacitidine and decitabine.EMBO reports · 2026Article
- DNA methyltransferase 1 correlates with immune modulation in pancreatic neuroendocrine tumors.Scientific reports · 2025Article
- Activation-induced cytidine deaminase in tertiary lymphoid structures: dual roles and implications in cancer prognosis.Frontiers in oncology · 2025Review
- The type of DNA damage response after decitabine treatment depends on the level of DNMT activity.Life science alliance · 2024Article
- Upregulation of TET2 and Resistance to DNA Methyltransferase (DNMT) Inhibitors inDiseases (Basel, Switzerland) · 2024Article
- Transcription-coupled DNA-protein crosslink repair by CSB and CRL4Nature cell biology · 2024Article
- The genome-wide mutational consequences of DNA hypomethylation.Scientific reports · 2023Article
- SMC5/6 complex-mediated SUMOylation stimulates DNA-protein cross-link repair in Arabidopsis.The Plant cell · 2023Article
- DNA damage, demethylation and anticancer activity of DNA methyltransferase (DNMT) inhibitors.Scientific reports · 2023Article
- SPRTN patient variants cause global-genome DNA-protein crosslink repair defects.Nature communications · 2023Article
- The off-target effects of AID in carcinogenesis.Frontiers in immunology · 2023Review
- Mitochondrial epigenetics in aging and cardiovascular diseases.Frontiers in cardiovascular medicine · 2023Review
- Isolation and Immunodetection of Enzymatic DNA-Protein Crosslinks by RADAR Assay.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Targeting DNA-Protein CrosslinksFrontiers in molecular biosciences · 2022Review
- 5-Aza-4'-thio-2'-deoxycytidine, a New Orally Bioavailable Nontoxic "Best-in-Class": DNA Methyltransferase 1-Depleting Agent in Clinical Development.The Journal of pharmacology and experimental therapeutics · 2021Review
- Replication-dependent cytotoxicity and Spartan-mediated repair of trapped PARP1-DNA complexes.Nucleic acids research · 2021Article
- Perspectives on PARP inhibitors as pharmacotherapeutic strategies for breast cancer.Expert opinion on pharmacotherapy · 2021Review
- Mechanisms of damage tolerance and repair during DNA replication.Nucleic acids research · 2021Review
- DNA-protein crosslink proteases in genome stability.Communications biology · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Observations that genome-wide DNA hypomethylation induces genome instability and tumors in animals caution against the indiscriminate use of demethylating agents, such as 5-aza-2'-deoxycytidine (5-Aza-dC). Using primary mouse embryonic fibroblasts harboring a lacZ mutational reporter construct that allows the quantification and characterization of a wide range of mutational events, we found that, in addition to demethylation, treatment with 5-Aza-dC induces γ-H2AX expression, a marker for DNA breaks, and both point mutations and genome rearrangements. To gain insight into the source of these mutations, we first tested the hypothesis that the mutagenic effect of 5-Aza-dC may be directly mediated through the DNA methyltransferase 1 (DNMT1) covalently trapped in 5-Aza-dC-substituted DNA. Knockdown of DNMT1 resulted in increased resistance to the cytostatic effects of 5-Aza-dC, delayed onset of γ-H2AX expression and a significant reduction in the frequency of genome rearrangements. There was no effect on the 5-Aza-dC-induced point mutations. An alternative mechanism for 5-Aza-dC-induced demethylation and genome rearrangements via activation-induced cytidine deaminase (AID) followed by base excision repair (BER) was found not to be involved. That is, 5-Aza-dC treatment did not significantly induce AID expression and inhibition of BER did not reduce the frequency of genome rearrangements. Thus, our results indicate that the formation of DNMT1 adducts is the prevalent mechanism of 5-Aza-dC-induced genome rearrangements, although hypomethylation per se may still contribute. As the therapeutic effects of 5-Aza-dC greatly depend on the presence of DNMT1, the expression level of DNA methyltransferases in tumors may serve as a prognostic factor for the efficacy of 5-Aza-dC treatment.
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Identifiers
What OpenQuestion holds
Registered trials
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.