ArticleOncotarget2015
HDAC1,2 inhibition impairs EZH2- and BBAP-mediated DNA repair to overcome chemoresistance in EZH2 gain-of-function mutant diffuse large B-cell lymphoma.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 39 citations in OpenAlex.
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- DTX3L promotes ovarian cancer progression and cisplatin resistance by activating JAK1/STAT1/OAS3 pathway.Scientific reports · 2026Article
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- Investigating the functions and molecular mechanisms of DTX3L in cancer progression.Frontiers in oncology · 2026Review
- Chromatin lysine acylation: On the path to chromatin homeostasis and genome integrity.Cancer science · 2024Review
- End binding-3 inhibitor activates regenerative program in age-related macular degeneration.Cell reports. Medicine · 2023Article
- Histone post-translational modification and the DNA damage response.Genes & diseases · 2023Review
- Post-Translational Modifications by Lipid Metabolites during the DNA Damage Response and Their Role in Cancer.Biomolecules · 2022Review
- A toolbox for class I HDACs reveals isoform specific roles in gene regulation and protein acetylation.PLoS genetics · 2022Article
- Lymphoid-specific helicase in epigenetics, DNA repair and cancer.British journal of cancer · 2022Review
- Review
- Targeting DNA Repair Pathways in Hematological Malignancies.International journal of molecular sciences · 2020Review
- Deficient histone H3 propionylation by BRPF1-KAT6 complexes in neurodevelopmental disorders and cancer.Science advances · 2020Article
- EZH2 abnormalities in lymphoid malignancies: underlying mechanisms and therapeutic implications.Journal of hematology & oncology · 2019Review
- NuclearCirculation · 2019Article
- Clinical significance of enhancer of zeste homolog 2 and histone deacetylases 1 and 2 expression in peripheral T-cell lymphoma.Oncology letters · 2019Article
- Assessment of epigenetic mechanisms and DNA double-strand break repair using laser micro-irradiation technique developed for hematological cells.EBioMedicine · 2019Article
- Article
- RBM45 competes with HDAC1 for binding to FUS in response to DNA damage.Nucleic acids research · 2017Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
Gain-of-function mutations in the catalytic site of EZH2 (Enhancer of Zeste Homologue 2), is observed in about 22% of diffuse large B-cell lymphoma (DLBCL) cases. Here we show that selective inhibition of histone deacetylase 1,2 (HDAC1,2) activity using a small molecule inhibitor causes cytotoxic or cytostatic effects in EZH2 gain-of-function mutant (EZH2GOF) DLBCL cells. Our results show that blocking the activity of HDAC1,2 increases global H3K27ac without causing a concomitant global decrease in H3K27me3 levels. Our data shows that inhibition of HDAC1,2 is sufficient to decrease H3K27me3 present at DSBs, decrease DSB repair and activate the DNA damage response in these cells. In addition to increased H3K27me3, we found that the EZH2GOF DLBCL cells overexpress another chemotherapy resistance factor - B-lymphoma and BAL-associated protein (BBAP). BBAP monoubiquitinates histone H4K91, a residue that is also subjected to acetylation. Our results show that selective inhibition of HDAC1,2 increases H4K91ac, decreases BBAP-mediated H4K91 monoubiquitination, impairs BBAP-dependent DSB repair and sensitizes the refractory EZH2GOF DLBCL cells to treatment with doxorubicin, a chemotherapy agent. Hence, selective HDAC1,2 inhibition provides a novel DNA repair mechanism-based therapeutic approach as it can overcome both EZH2- and BBAP-mediated DSB repair in the EZH2GOF DLBCL cells.
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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.