UV-induced histone H2AX phosphorylation and DNA damage related proteins accumulate and persist in nucleotide excision repair-deficient XP-B cells
Open accessAbstract
DNA double strand breaks (DSB) may be caused by ionizing radiation. In contrast, UV exposure forms dipyrimidine photoproducts and is not considered an inducer of DSB. We found that uniform or localized UV treatment induced phosphorylation of the DNA damage related (DDR) proteins H2AX, ATM and NBS1 and co-localization of γ-H2AX with the DDR proteins p-ATM, p-NBS1, Rad51 and FANCD2 that persisted for about 6h in normal human fibroblasts. This post-UV phosphorylation was observed in the absence of nucleotide excision repair (NER), since NER deficient XP-B cells (lacking functional XPB DNA repair helicase) and global genome repair-deficient rodent cells also showed phosphorylation and localization of these DDR proteins. Resolution of the DDR proteins was dependent on NER, since they persisted for 24h in the XP-B cells. In the normal and XP-B cells p53 and p21 was detected at 6h and 24h but Mdm2 was not induced in the XP-B cells. Post-UV induction of Wip1 phosphatase was detected in the normal cells but not in the XP-B cells. DNA DSB were detected with a neutral comet assay at 6h and 24h post-UV in the normal and XP-B cells. These results indicate that UV damage can activate the DDR pathway in the absence of NER. However, a later step in DNA damage processing involving induction of Wip1 and resolution of DDR proteins was not observed in the absence of NER.
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Oh et al. reported that γH2AX foci form after UV irradiation in cells lacking NER.
“Recently, Oh et. al. reported γH2AX foci formation after UV-irradiation in cells lacking NER [32].”
From NER initiation factors, DDB2 and XPC, regulate UV radiation response by recruiting ATR and ATM kinases to DNA damage sites (2013) · cites this paper as [32]
In XPB-deficient cells, UV treatment induces phosphorylation of H2AX, ATM, and NBS1.
“UV-induced phosphorylation of H2AX, ATM, and NBS1 was observed in XPB-deficient cells”
From Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress (2014) · cites this paper as [201]
Transcription-coupled NER may not be required for ATM checkpoint signaling.
“suggesting TC-NER may be dispensable for ATM checkpoint signaling [201]”
From Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress (2014) · cites this paper as [201]
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“The UV damaged foci exhibited the distinct phosphorylation of H2AX, a recognized molecular marker of damage response initiation [19, 32, 35-37].”
BackgroundWakasugi, M., Sasaki, T., Matsumoto, M., Nagaoka, M., Inoue, K., Inobe, M., Horibata, K., Tanaka, K., & Matsunaga, T. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.589747 · Cited by 48 · see citing works
- Authors
- Oh, K.-S., Bustin, M., Mazur, S. J., Appella, E., & Kraemer, K. H.
- Affiliations
- National Cancer Institute (US)
- National Institutes of Health (US)
- Corresponding author
- Kraemer, Kenneth H.
- Venue
- DNA Repair
- Publisher
- Elsevier BV
- Published
- 2011-01-02
- Volume
- 10
- Issue
- 1
- Pages
- 5-15
- ISSN
- 1568-7856 (ISSN-L)
- 1568-7864
- PMC
- PMC3010519
- OpenAlex
- W2025993893
- Cited by
- 60
- References
- 57
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 3 · 2023: 4 · 2022: 4 · 2021: 3 · 2020: 3 · 2019: 4 · 2018: 3 · 2017: 3 · 2016: 7 · 2015: 3 · 2014: 5 · 2013: 3 · 2012: 6
- FWCI
- 1.82
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- DNA repair (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging
- National Cancer Institute (ZIABC004517)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
- Keywords
- UV-induced DNA damage, DNA double-strand breaks, DNA damage response, H2AX phosphorylation, ATM phosphorylation, NBS1, RAD51, FANCD2, nucleotide excision repair deficiency, XPB helicase, Wip1 phosphatase, p53, p21, MDM2, global genome repair
- MeSH terms
- Protein Phosphatase 2C, Animals, Cell Line, DNA Damage, DNA Repair, DNA-Binding Proteins, Fibroblasts, Histones, Humans, Mutation, Nuclear Proteins, Phosphoprotein Phosphatases, Phosphorylation, Time Factors, Ultraviolet Rays, Apoptosis, Protein Serine-Threonine Kinases, Cell Cycle Proteins, Fluorescent Antibody Technique, Indirect, Comet Assay, Tumor Suppressor Proteins, Mice, DNA Breaks, Double-Stranded, Ataxia Telangiectasia Mutated Proteins
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