ArticleCancer research2010
Inhibition of histone deacetylase in cancer cells slows down replication forks, activates dormant origins, and induces DNA damage.
Article in Cancer research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers.
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.
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Who cites it
97 citing papers in PubMed, 155 citations in OpenAlex.
- Clinical Trials Assessing Hypomethylating Agents Combined with Other Therapies: Causes for Failure and Potential Solutions.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Trial
- Oral tetrahydrouridine and decitabine for non-cytotoxic epigenetic gene regulation in sickle cell disease: A randomized phase 1 study.PLoS medicine · 2017Trial
- Romidepsin in peripheral and cutaneous T-cell lymphoma: mechanistic implications from clinical and correlative data.British journal of haematology · 2015Trial
- The antiparasitic clioquinol induces apoptosis in leukemia and myeloma cells by inhibiting histone deacetylase activity.The Journal of biological chemistry · 2013Trial
- How histone modifications influence cellular radiosensitivity: Pharmaceutically targeting epigenetic regulators as a promising avenue to overcome radioresistance.Acta pharmaceutica Sinica. B · 2025Review
- Inhibition of Histone Deacetylases Induces Cancer Cell Apoptosis Through the PERK Pathway of ER Stress Response.Journal of cellular and molecular medicine · 2025Article
- Harnessing Epigenetics: Innovative Approaches in Diagnosing and Combating Viral Acute Respiratory Infections.Pathogens (Basel, Switzerland) · 2025Review
- SIN3A histone deacetylase action counteracts MUS81 to promote stalled fork stability.Cell reports · 2024Article
- Reversion from basal histone H4 hypoacetylation at the replication fork increases DNA damage in FANCA deficient cells.PloS one · 2024Article
- Introducing HDAC-Targeting Radiopharmaceuticals for Glioblastoma Imaging and Therapy.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Case Report: Outcome and Adverse Events of Anti-PD-1 Antibody Plus Chidamide for Relapsed/Refractory Sézary Syndrome: Case Series and A Literature Review.Frontiers in oncology · 2022Article
- Targeted Cancer Therapy Based on Acetylation and Deacetylation of Key Proteins Involved in Double-Strand Break Repair.Cancer management and research · 2022Review
- Histone acetylation modifications: A potential targets for the diagnosis and treatment of papillary thyroid cancer.Frontiers in oncology · 2022Review
- Identification of a novel pyridine derivative with inhibitory activity against ovarian cancer progressionFrontiers in pharmacology · 2022Article
- R-Loop-Mediated ssDNA Breaks Accumulate Following Short-Term Exposure to the HDAC Inhibitor Romidepsin.Molecular cancer research : MCR · 2021Article
- Review
- Entinostat, a selective HDAC1/2 inhibitor, potentiates the effects of olaparib in homologous recombination proficient ovarian cancer.Gynecologic oncology · 2021Article
- FK228 sensitizes radioresistant small cell lung cancer cells to radiation.Clinical epigenetics · 2021Article
- Resolution of R-loops by INO80 promotes DNA replication and maintains cancer cell proliferation and viability.Nature communications · 2020Article
- Discovery of histone deacetylase 3 (HDAC3)-specific PROTACs.Chemical communications (Cambridge, England) · 2020Article
37 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Protein acetylation is a reversible process regulated by histone deacetylases (HDAC) that is often altered in human cancers. Suberoylanilide hydroxamic acid (SAHA) is the first HDAC inhibitor to be approved for clinical use as an anticancer agent. Given that histone acetylation is a key determinant of chromatin structure, we investigated how SAHA may affect DNA replication and integrity to gain deeper insights into the basis for its anticancer activity. Nuclear replication factories were visualized with confocal immunofluorescence microscopy and single-replicon analyses were conducted by genome-wide molecular combing after pulse labeling with two thymidine analogues. We found that pharmacologic concentrations of SAHA induce replication-mediated DNA damage with activation of histone gammaH2AX. Single DNA molecule analyses indicated slowdown in replication speed along with activation of dormant replication origins in response to SAHA. Similar results were obtained using siRNA-mediated depletion of HDAC3 expression, implicating this HDAC member as a likely target in the SAHA response. Activation of dormant origins was confirmed by molecular analyses of the beta-globin locus control region. Our findings demonstrate that SAHA produces profound alterations in DNA replication that cause DNA damage, establishing a critical link between robust chromatin acetylation and DNA replication in human cancer cells.
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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.