ArticleEpigenetics & chromatin2013
Histone deacetylases 1 and 2 maintain S-phase chromatin and DNA replication fork progression.
Article in Epigenetics & chromatin, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 70 citations in OpenAlex.
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- HAT1 Regulates Intestinal Stem Cell Proliferation and Differentiation.bioRxiv : the preprint server for biology · 2026Article
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- Acetylation-Mediated Epigenetic Consequences for Biological Control and Cancer.Results and problems in cell differentiation · 2025Review
- SIN3A histone deacetylase action counteracts MUS81 to promote stalled fork stability.Cell reports · 2024Article
- Entinostat Enhances the Efficacy of Chemotherapy in Small Cell Lung Cancer Through S-phase Arrest and Decreased Base Excision Repair.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- OTUD5 limits replication fork instability by organizing chromatin remodelers.Nucleic acids research · 2023Article
- Human SMARCA5 is continuously required to maintain nucleosome spacing.Molecular cell · 2023Article
- Rational Combinations of PARP Inhibitors with HRD-Inducing Molecularly Targeted Agents.Cancer treatment and research · 2023Review
- Single-Cell Analysis of Histone Acetylation Dynamics at Replication Forks Using PLA and SIRF.Methods in molecular biology (Clifton, N.J.) · 2023Article
- A toolbox for class I HDACs reveals isoform specific roles in gene regulation and protein acetylation.PLoS genetics · 2022Article
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- SNP rs4971059 predisposes to breast carcinogenesis and chemoresistance via TRIM46-mediated HDAC1 degradation.The EMBO journal · 2021Article
- Bromodomain proteins: protectors against endogenous DNA damage and facilitators of genome integrity.Experimental & molecular medicine · 2021Review
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Corrections and comments
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHistone deacetylases (HDACs) play a critical role in the maintenance of genome stability. Class I HDACs, histone deacetylase 1 and 2 (Hdac1 and Hdac2) are recruited to the replication fork by virtue of their interactions with the replication machinery. However, functions for Hdac1 and Hdac2 (Hdacs1,2) in DNA replication are not fully understood.
resultsUsing genetic knockdown systems and novel Hdacs1,2-selective inhibitors, we found that loss of Hdacs1,2 leads to a reduction in the replication fork velocity, and an increase in replication stress response culminating in DNA damage. These observed defects are due to a direct role for Hdacs1,2 in DNA replication, as transcription of genes involved in replication was not affected in the absence of Hdacs1,2. We found that loss of Hdacs1,2 functions increases histone acetylation (ac) on chromatin in S-phase cells and affects nascent chromatin structure, as evidenced by the altered sensitivity of newly synthesized DNA to nuclease digestion. Specifically, H4K16ac, a histone modification involved in chromatin decompaction, is increased on nascent chromatin upon abolishing Hdacs1,2 activities. It was previously shown that H4K16ac interferes with the functions of SMARCA5, an ATP-dependent ISWI family chromatin remodeler. We found SMARCA5 also associates with nascent DNA and loss of SMARCA5 decreases replication fork velocity similar to the loss or inhibition of Hdacs1,2.
conclusionsOur studies reveal important roles for Hdacs1,2 in nascent chromatin structure maintenance and regulation of SMARCA5 chromatin-remodeler function, which together are required for proper replication fork progression and genome stability in S-phase.
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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.