Cell cycle arrest and apoptosis provoked by UV radiation-induced DNA damage are transcriptionally highly divergent responses
Open accessAbstract
DNA damage caused by UV radiation initiates cellular recovery mechanisms, which involve activation of DNA damage response pathways, cell cycle arrest and apoptosis. To assess cellular transcriptional responses to UVC-induced DNA damage we compared time course responses of human skin fibroblasts to low and high doses of UVC radiation known to induce a transient cellular replicative arrest or apoptosis, respectively. UVC radiation elicited >3-fold changes in 460 out of 12,000 transcripts and 89% of these represented downregulated transcripts. Only 5% of the regulated genes were common to both low and high doses of radiation. Cells inflicted with a low dose of UVC exhibited transcription profiles demonstrating transient regulation followed by recovery, whereas the responses were persistent after the high dose. A detailed clustering analysis and functional classification of the targets implied regulation of biologically divergent responses and suggested involvement of transcriptional and translational machinery, inflammatory, anti-proliferative and anti-angiogenic responses. The data support the notion that UVC radiation induces prominent, dose-dependent downregulation of transcription. However, the data strongly suggest that transcriptional repression is also target gene selective. Furthermore, the results demonstrate that dose-dependent induction of cell cycle arrest and apoptosis by UVC radiation are transcriptionally highly distinct responses.
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Defects in DNA damage response are the underlying cause of many human diseases.
“Defects in DNA damage response are the underlying cause of multitude human disease [52,146,147,148].”
From Focus on UV-Induced DNA Damage and Repair—Disease Relevance and Protective Strategies (2020) · cites this paper as [52]
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- Authors
- Gentile, M.
- Affiliations
- University of Helsinki (FI)
- Corresponding author
- Gentile, M.
- Venue
- Nucleic Acids Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2003-08-15
- Volume
- 31
- Issue
- 16
- Pages
- 4779-4790
- ISSN
- 0305-1048 (ISSN-L)
- 1362-4962
- PMC
- PMC169943
- OpenAlex
- W2127702552
- Cited by
- 185
- References
- 47
- Citations by year
- 2026: 6 · 2025: 7 · 2024: 10 · 2023: 14 · 2022: 11 · 2021: 7 · 2020: 11 · 2019: 9 · 2018: 6 · 2017: 6 · 2016: 9 · 2015: 8 · 2014: 5 · 2013: 13 · 2012: 16
- FWCI
- 1.03
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Nucleic Acids Research (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Health Sciences › Medicine › Dermatology › Skin Protection and Aging
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
- Keywords
- UV-C radiation, UV-induced DNA damage, cell cycle arrest, apoptosis, transcriptional response, dermal fibroblasts, DNA damage response, inflammation, transcriptional repression
- MeSH terms
- Cell Cycle, Cell Line, DNA Damage, Dose-Response Relationship, Radiation, Fibroblasts, Gene Expression Regulation, Humans, RNA, Skin, Transcription, Genetic, Ultraviolet Rays, Blotting, Northern, Cluster Analysis, Apoptosis, Oligonucleotide Array Sequence Analysis
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