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HDAC3 Is Required for XPC Recruitment and Nucleotide Excision Repair of DNA Damage Induced by UV Irradiation
Open accessPublished version of a preprint
Abstract
Recent studies have demonstrated that lysine acetylation of histones is crucial for nucleotide excision repair (NER) by relaxing the chromatin structure, which facilitates the recruitment of repair factors. However, few studies have focused on the contribution of histone deacetylases (HDAC) to NER. Here, we found that histone H3 Lys14 (H3K14) was deacetylated by HDAC3 after UV irradiation. Depletion of HDAC3 caused defects in cyclobutene pyrimidine dimer excision and sensitized cells to UV irradiation. HDAC3-depleted cells had impaired unscheduled DNA synthesis, but not recovery of RNA synthesis, which indicates that HDAC3 was required for global genome NER. Moreover, xeroderma pigmentosum, complementation group C (XPC) accumulation at the local UV-irradiated area was attenuated in HDAC3-depleted cells. In addition to the delay of XPC accumulation at DNA damage sites, XPC ubiquitylation was inhibited in HDAC3-depleted cells. These results suggest that the deacetylation of histone H3K14 by HDAC3 after UV irradiation contributes to XPC recruitment to DNA lesions to promote global genome NER. IMPLICATIONS: Involvement of histone deacetylation for XPC accumulation after UV irradiation indicates conversion of chromatin structure is essential for nucleotide excision repair in human cancer cells.
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“The dynamics of H3K14ac may be critical for the temporal recruitment of elements of the repair machinery (Nishimoto et al., 2020).”
From HDACs and the epigenetic plasticity of cancer cells: target the complexity (2022) · cites this paper as Nishimoto et al., 2020
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UV-Induced Ubiquitylation of XPC Protein Mediated by UV-DDB-Ubiquitin Ligase Complex
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Adhikari, N., Jha, T., & Ghosh, B. (2021) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c01676 · Cited by 74
Characterization of Histone Deacetylase Mechanisms in Cancer Development
Hai, R., He, L., Shu, G., & Yin, G. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.700947 · Cited by 69
HDACs and the epigenetic plasticity of cancer cells: target the complexity
Brancolini, C., Gagliano, T., & Minisini, M. (2022) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2022.108190 · Cited by 55
Nucleotide excision repair leaves a mark on chromatin: DNA damage detection in nucleosomes
Apelt, K., Lans, H., Schärer, O. D., & Luijsterburg, M. S. (2021) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-021-03984-7 · Cited by 45
Natural Bioactive Compounds Targeting Histone Deacetylases in Human Cancers: Recent Updates
Bouyahya, A., Hachlafi, N. E., Aanniz, T., Bourais, I., Mechchate, H., Benali, T., Shariati, M. A., Burkov, P., Lorenzo, J. M., Wilairatana, P., et al. (2022) · Molecules · doi:10.3390/molecules27082568 · Cited by 41
Metadata
- Authors
- Nishimoto, K., Niida, H., Uchida, C., Ohhata, T., Kitagawa, K., Motegi, A., Suda, T., & Kitagawa, M.
- Affiliations
- Hamamatsu University (JP)
- Kyoto University (JP)
- ORCID
- Venue
- Molecular Cancer Research
- Published
- 2020-09-01
- Volume
- 18
- Issue
- 9
- Pages
- 1367-1378
- ISSN
- 1541-7786 (ISSN-L)
- 1557-3125
- OpenAlex
- W3034813007
- Cited by
- 21
- References
- 50
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 4 · 2023: 2 · 2022: 5 · 2021: 6
- FWCI
- 1.05
- Type
- journal article
- Language
- en
- Open access
- Licence
- cc-by-nc-nd
- Locations
- Molecular Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion, cc-by-nc-nd)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology of Japan (16K08580, 25290044)
- Uehara Memorial Foundation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- HDAC3, histone deacetylase, nucleotide excision repair, XPC, UV irradiation, global genome repair, chromatin structure, unscheduled DNA synthesis, DNA damage response
- MeSH terms
- Histone Deacetylase 3, DNA Damage, DNA Repair, DNA-Binding Proteins, HeLa Cells, Histone Deacetylases, Humans, Ultraviolet Rays
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