ArticleBiology open2015
Overexpression of KDM4 lysine demethylases disrupts the integrity of the DNA mismatch repair pathway.
Article in Biology open, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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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.
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Who cites it
24 citing papers in PubMed, 36 citations in OpenAlex.
- XPC Deficiency Activate Cisplatin-Mediated Autophagy in Bladder Cancer by Limiting Novel PHRF1-Mediated Ubiquitination of the p53 Protein.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Phase 1 study of zavondemstat (TACH101), a first-in-class KDM4 inhibitor, in patients with advanced solid tumors.The oncologist · 2025Article
- Review
- Epigenetics, DNA damage, and aging.The Journal of clinical investigation · 2022Review
- Orc6 is a component of the replication fork and enables efficient mismatch repair.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Mechanistic insights into KDM4A driven genomic instability.Biochemical Society transactions · 2021Review
- H3K36me3, message from chromatin to DNA damage repair.Cell & bioscience · 2020Review
- DNA mismatch repair in the context of chromatin.Cell & bioscience · 2020Review
- Microsatellite Instability: Diagnosis, Heterogeneity, Discordance, and Clinical Impact in Colorectal Cancer.Cancers · 2019Review
- Genome-wide Kdm4 histone demethylase transcriptional regulation in Drosophila.Molecular genetics and genomics : MGG · 2019Article
- miR675 Accelerates Malignant Transformation of Mesenchymal Stem Cells by Blocking DNA Mismatch Repair.Molecular therapy. Nucleic acids · 2019Article
- Timely double-strand break repair and pathway choice in pericentromeric heterochromatin depend on the histone demethylase dKDM4A.Genes & development · 2019Article
- Unraveling KDM4 histone demethylase expression and its association with adverse cytogenetic findings in chronic lymphocytic leukemia.Medical oncology (Northwood, London, England) · 2018Article
- Cancer-driving H3G34V/R/D mutations block H3K36 methylation and H3K36me3-MutSα interaction.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Histone demethylase KDM4D promotes gastrointestinal stromal tumor progression through HIF1β/VEGFA signalling.Molecular cancer · 2018Article
- Drosophila Histone Demethylase KDM4A Has Enzymatic and Non-enzymatic Roles in Controlling Heterochromatin Integrity.Developmental cell · 2017Article
- Rare germline alterations in cancer-related genes associated with the risk of multiple primary tumor development.Journal of molecular medicine (Berlin, Germany) · 2017Article
- SETting the Stage for Cancer Development: SETD2 and the Consequences of Lost Methylation.Cold Spring Harbor perspectives in medicine · 2017Review
- JMJD-5/KDM8 regulates H3K36me2 and is required for late steps of homologous recombination and genome integrity.PLoS genetics · 2017Article
- Structure/Function Analysis of Recurrent Mutations in SETD2 Protein Reveals a Critical and Conserved Role for a SET Domain Residue in Maintaining Protein Stability and Histone H3 Lys-36 Trimethylation.The Journal of biological chemistry · 2016Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The KDM4 family of lysine demethylases consists of five members, KDM4A, -B and -C that demethylate H3K9me2/3 and H3K36me2/3 marks, while KDM4D and -E demethylate only H3K9me2/3. Recent studies implicated KDM4 proteins in regulating genomic instability and carcinogenesis. Here, we describe a previously unrecognized pathway by which hyperactivity of KDM4 demethylases promotes genomic instability. We show that overexpression of KDM4A-C, but not KDM4D, disrupts MSH6 foci formation during S phase by demethylating its binding site, H3K36me3. Consequently, we demonstrate that cells overexpressing KDM4 members are defective in DNA mismatch repair (MMR), as evident by the instability of four microsatellite markers and the remarkable increase in the spontaneous mutations frequency at the HPRT locus. Furthermore, we show that the defective MMR in cells overexpressing KDM4C is mainly due to the increase in its demethylase activity and can be mended by KDM4C downregulation. Altogether, our data suggest that cells overexpressing KDM4A-C are defective in DNA MMR and this may contribute to genomic instability and tumorigenesis.
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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.