Role of poly(ADP-ribose) polymerase-1 in the removal of UV-induced DNA lesions by nucleotide excision repair
Open accessAbstract
Among the earliest responses of mammalian cells to DNA damage is catalytic activation of a nuclear enzyme poly(ADP-ribose) polymerase-1 (PARP-1). Activated PARP-1 forms the polymers of ADP-ribose (pADPr or PAR) that posttranslationally modify its target proteins, such as PARP-1 and DNA repair–related proteins. Although this metabolism is known to be implicated in other repair pathways, here we show its role in the versatile nucleotide excision repair pathway (NER) that removes a variety of DNA damages including those induced by UV. We show that PARP inhibition or specific depletion of PARP-1 decreases the efficiency of removal of UV-induced DNA damage from human skin fibroblasts or mouse epidermis. Using NER-proficient and -deficient cells and in vitro PARP-1 assays, we show that damaged DNA-binding protein 2 (DDB2), a key lesion recognition protein of the global genomic subpathway of NER (GG-NER), associates with PARP-1 in the vicinity of UV-damaged chromatin, stimulates its catalytic activity, and is modified by pADPr. PARP inhibition abolishes UV-induced interaction of DDB2 with PARP-1 or xeroderma pigmentosum group C (XPC) and also decreases localization of XPC to UV-damaged DNA, which is a key step that leads to downstream events in GG-NER. Thus, PARP-1 collaborates with DDB2 to increase the efficiency of the lesion recognition step of GG-NER.
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Inhibition or depletion of PARP1 significantly deteriorates UV-damage removal in human skin fibroblasts and epidermis.
“Furthermore, inhibition or depletion of PARP1 significantly deteriorates UV-damage removal in human skin fibroblasts and epidermis.”
From Focus on UV-Induced DNA Damage and Repair—Disease Relevance and Protective Strategies (2020) · cites this paper as [69]
The reduced NER activity in the absence of PARP1 may result from lack of interaction between DDB2 or XPC and PARP1 in the presence of UV damage, affecting damage recognition.
“The reduced NER activity may result from the lack of interaction between key lesion recognizer—damaged DNA-binding protein 2 (DDB2) or xeroderma pigmentosum group C (XPC) and PARP1 in the presence of UV damage affecting damage recognition [69].”
From Focus on UV-Induced DNA Damage and Repair—Disease Relevance and Protective Strategies (2020) · cites this paper as [69]
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- Authors
- Robu, M., Shah, R. G., Petitclerc, N., Brind’Amour, J., Kandan-Kulangara, F., & Shah, G. M.
- Affiliations
- Centre hospitalier universitaire de Québec (CA)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2013-01-14
- Volume
- 110
- Issue
- 5
- Pages
- 1658-1663
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3562836
- OpenAlex
- W2094170505
- Cited by
- 177
- References
- 24
- Citations by year
- 2026: 7 · 2025: 6 · 2024: 8 · 2023: 11 · 2022: 17 · 2021: 18 · 2020: 9 · 2019: 9 · 2018: 10 · 2017: 20 · 2016: 20 · 2015: 21 · 2014: 9 · 2013: 12
- FWCI
- 9.25
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Université Laval
- Natural Sciences and Engineering Research Council of Canada
- National Cancer Institute
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Health Sciences › Medicine › Oncology › PARP inhibition in cancer therapy
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Keywords
- PARP1, nucleotide excision repair, UV-induced DNA damage, DDB2, XPC, PARP inhibition, DNA damage recognition, dermal fibroblasts, epidermis, DNA repair
- MeSH terms
- Poly(ADP-ribose) Polymerase Inhibitors, Animals, Cell Line, Transformed, DNA, DNA Damage, DNA Repair, DNA-Binding Proteins, Epidermis, Female, Fibroblasts, Humans, Mice, Hairless, Phenanthrenes, Poly(ADP-ribose) Polymerases, Protein Binding, Time Factors, Ultraviolet Rays, Immunoblotting, RNA Interference, Mice
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