ArticleMolecular and cellular biology2006
DNA methyltransferase 1 knockdown activates a replication stress checkpoint.
Article in Molecular and cellular biology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 97 citations in OpenAlex.
- Synthetic lethality of decitabine plus ATR inhibition for TP53-mutated AML.Blood advances · 2026Article
- Disrupting the epigenetic alliance: structural insights and therapeutic strategies targeting DNMT1-UHRF1.Functional & integrative genomics · 2025Review
- Article
- DNMT3b-mediated CpA methylation facilitates REST binding and gene silencing and exacerbates hippocampal demyelination in diabetic mice.The Journal of biological chemistry · 2025Article
- DNMT1 prolonged absence is a tunable cellular stress that triggers cell proliferation arrest to protect from major DNA methylation loss.Cellular and molecular life sciences : CMLS · 2024Article
- NS1-mediated DNMT1 degradation regulates human bocavirus 1 replication and RNA processing.PLoS pathogens · 2024Article
- DNA hypomethylation activates Cdk4/6 and Atr to induce DNA replication and cell cycle arrest to constrain liver outgrowth in zebrafish.Nucleic acids research · 2024Article
- DNMT1 mutant ants develop normally but have disrupted oogenesis.Nature communications · 2023Article
- Hypermethylation of ACADVL is involved in the high-intensity interval training-associated reduction of cardiac fibrosis in heart failure patients.Journal of translational medicine · 2023Article
- Aging Effects on Optic Nerve Neurodegeneration.International journal of molecular sciences · 2023Review
- Epigenetic Regulation of Optic Nerve Development, Protection, and Repair.International journal of molecular sciences · 2022Review
- Gene by environment interaction mouse model reveals a functional role for 5-hydroxymethylcytosine in neurodevelopmental disorders.Genome research · 2022Article
- Deciphering the synergistic and redundant roles of CG and non-CG DNA methylation in plant development and transposable element silencing.The New phytologist · 2022Article
- Novel Targeting of DNA Methyltransferase Activity Inhibits Ewing Sarcoma Cell Proliferation and Enhances Tumor Cell Sensitivity to DNA Damaging Drugs by Activating the DNA Damage Response.Frontiers in endocrinology · 2022Article
- Review
- dnmt1 function is required to maintain retinal stem cells within the ciliary marginal zone of the zebrafish eye.Scientific reports · 2020Article
- Article
- Effects of 5-aza-2´-deoxycytidine on primary human chondrocytes from osteoarthritic patients.PloS one · 2020Article
- Differences in MWCNT- and SWCNT-induced DNA methylation alterations in association with the nuclear deposition.Particle and fibre toxicology · 2018Article
- DNA methylation in development and disease: an overview for prostate researchers.American journal of clinical and experimental urology · 2018Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
DNA methyltransferase 1 (DNMT1) is an important component of the epigenetic machinery and is responsible for copying DNA methylation patterns during cell division. Coordination of DNA methylation and DNA replication is critical for maintaining epigenetic programming. Knockdown of DNMT1 leads to inhibition of DNA replication, but the mechanism has been unclear. Here we show that depletion of DNMT1 with either antisense or small interfering RNA (siRNA) specific to DNMT1 activates a cascade of genotoxic stress checkpoint proteins, resulting in phosphorylation of checkpoint kinases 1 and 2 (Chk1 and -2), gammaH2AX focus formation, and cell division control protein 25a (CDC25a) degradation, in an ataxia telangiectasia mutated-Rad3-related (ATR)-dependent manner. siRNA knockdown of ATR blocks the response to DNMT1 depletion; DNA synthesis continues in the absence of DNMT1, resulting in global hypomethylation. Similarly, the response to DNMT1 knockdown is significantly attenuated in human mutant ATR fibroblast cells from a Seckel syndrome patient. This response is sensitive to DNMT1 depletion, independent of the catalytic domain of DNMT1, as indicated by abolition of the response with ectopic expression of either DNMT1 or DNMT1 with the catalytic domain deleted. There is no response to short-term treatment with 5-aza-deoxycytidine (5-aza-CdR), which causes demethylation by trapping DNMT1 in 5-aza-CdR-containing DNA but does not cause disappearance of DNMT1 from the nucleus. Our data are consistent with the hypothesis that removal of DNMT1 from replication forks is the trigger for this response.
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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.