ArticleScientific reports2018
The DNMT3A R882H mutation does not cause dominant negative effects in purified mixed DNMT3A/R882H complexes.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 34 citations in OpenAlex.
- DNMT3A in cancer: from epigenetic writer to oncogenic driver.Clinical epigenetics · 2026Review
- Local Promoter Methylation Disorder algorithm reveals bidirectional epigenetic disruption in DNMT3A-mutated AML and predicts azacitidine treatment response.Frontiers in oncology · 2026Article
- Double mutant DNMT3A AML: a unique subtype experiencing increased DNA damage and poor prognosis.Blood advances · 2025Article
- Clonal hematopoiesis and hematological malignancy.The Journal of clinical investigation · 2024Review
- Structure-guided functional suppression of AML-associated DNMT3A hotspot mutations.Nature communications · 2024Article
- DNMT3A Cooperates with YAP/TAZ to Drive Gallbladder Cancer Metastasis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Distinct disease mutations in DNMT3A result in a spectrum of behavioral, epigenetic, and transcriptional deficits.Cell reports · 2023Article
- Distinct disease mutations in DNMT3A result in a spectrum of behavioral, epigenetic, and transcriptional deficits.bioRxiv : the preprint server for biology · 2023Article
- Unveiling the methyl transfer mechanisms in the epigenetic machinery DNMT3A-3 L: A comprehensive study integrating assembly dynamics with catalytic reactions.Computational and structural biotechnology journal · 2023Article
- Mediating and maintaining methylation while minimizing mutation: Recent advances on mammalian DNA methyltransferases.Current opinion in structural biology · 2022Review
- Review
- Alterations toCancer research · 2021Review
- Comprehensive structure-function characterization of DNMT3B and DNMT3A reveals distinctive de novo DNA methylation mechanisms.Nature communications · 2020Article
- Structural basis for impairment of DNA methylation by the DNMT3A R882H mutation.Nature communications · 2020Article
- The Molecular Genetics of Myeloproliferative Neoplasms.Cold Spring Harbor perspectives in medicine · 2020Review
- Functional Analysis of DNMT3A DNA Methyltransferase Mutations Reported in Patients with Acute Myeloid Leukemia.Biomolecules · 2019Article
- Mutations of R882 change flanking sequence preferences of the DNA methyltransferase DNMT3A and cellular methylation patterns.Nucleic acids research · 2019Article
- The R882H DNMT3A hot spot mutation stabilizes the formation of large DNMT3A oligomers with low DNA methyltransferase activity.The Journal of biological chemistry · 2019Article
- A Model System for Studying the DNMT3A Hotspot Mutation (DNMT3ACancer research · 2019Article
- Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 2 countries.
Funding
Abstract
The DNA methyltransferase DNMT3A R882H mutation is observed in 25% of all AML patients. DNMT3A is active as tetramer and the R882H mutation is located in one of the subunit/subunit interfaces. Previous work has reported that formation of mixed wildtype/R882H complexes leads to a strong loss of catalytic activity observed in in vitro DNA methylation assays (Russler-Germain et al., 2014, Cancer Cell 25:442-454). To investigate this effect further, we have prepared mixed wildtype/R882H DNMT3A complexes by incubation of individually purified subunits of the DNMT3A catalytic domain and full-length DNMT3A2. In addition, we have used a double affinity tag approach and specifically purified mixed catalytic domain complexes formed after co-expression of R882H and wildtype subunits in E. coli cells. Afterwards, we determined the catalytic activity of the mixed complexes and compared it to that of purified complexes only consisting of one subunit type. In both settings, the expected catalytic activities of mixed R882H/wildtype complexes were observed demonstrating an absence of a dominant negative effect of the R882H mutation in purified DNMT3A enzymes. This result suggests that heterocomplex formation of DNMT3A and R882H is unlikely to cause dominant negative effects in human cells as well. The limitations of this conclusion and its implications are discussed.
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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.