Cellular Responses and Repair of Single-strand Breaks Introduced by UV Damage Endonuclease in Mammalian Cells
Open accessAbstract
Although single-strand breaks (SSBs) occur frequently, the cellular responses and repair of SSB are not well understood. To address this, we established mammalian cell lines expressing Neurospora crassa UV damage endonuclease (UVDE), which introduces a SSB with a 3'-OH immediately 5' to UV-induced cyclobutane pyrimidine dimers or 6-4 photoproducts and initiates an alternative excision repair process. Xeroderma pigmentosum group A cells expressing UVDE show UV resistance of almost the wild-type level. In these cells SSBs are produced upon UV irradiation and then efficiently repaired. The repair patch size is about seven nucleotides, and repair synthesis is decreased to 30% by aphidicolin, suggesting the involvement of a DNA polymerase delta/epsilon-dependent long-patch repair. Immediately after UV irradiation, cellular proteins are poly(ADP-ribosyl)ated. The UV resistance of the cells is decreased in the presence of 3-aminobenzamide, an inhibitor of poly(ADP-ribose) polymerase. Expression of UVDE in XRCC1-defective EM9, a Chinese hamster ovary cell line, greatly sensitizes the host cells to UV, and addition of 3-aminobenzamide results in almost no further sensitization of the cells to UV. Thus, we show that XRCC1 and PARP are involved in the same pathway for the repair of SSBs.
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Following UVB irradiation, UVDE-initiated repair results in rapid, long-patch processes, improving survival in DNA repair-deficient cells.
“Collectively, these data present consistent evidence that following UVB irradiation, UVDE-initiated repair results in rapid, long-patch processes, improving survival in DNA repair-deficient cells.”
From Modulation of UVB-induced Carcinogenesis by Activation of Alternative DNA Repair Pathways (2018) · cites this paper as [32]
In UV-irradiated XPA cells expressing Neurospora crassa UVDE, single-strand breaks were introduced immediately following irradiation and were efficiently repaired, resulting in enhanced survival approaching that of wild-type cells.
“Further, in UV-irradiated XPA cells expressing the Neurospora crassa UVDE, single-strand breaks were introduced immediately following irradiation and were efficiently repaired, resulting in enhanced survival approaching that of wild-type cells31,32.”
From Modulation of UVB-induced Carcinogenesis by Activation of Alternative DNA Repair Pathways (2018) · cites this paper as [32]
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- Authors
- Okano, S., Kanno, S.-I., Nakajima, S., & Yasui, A.
- Affiliations
- Tohoku University (JP)
- Corresponding author
- Yasui, Akira
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2000-10
- Volume
- 275
- Issue
- 42
- Pages
- 32635-32641
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2036496759
- Cited by
- 47
- References
- 36
- Citations by year
- 2024: 1 · 2023: 2 · 2021: 1 · 2020: 4 · 2018: 2 · 2017: 3 · 2015: 2 · 2014: 2 · 2013: 3 · 2012: 2
- FWCI
- 0.84
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- 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 › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
- Keywords
- single-strand break repair, Neurospora crassa, cyclobutane pyrimidine dimers, 6-4 photoproducts, long-patch repair, XPA, XRCC1, poly(ADP-ribose) polymerase, poly(ADP-ribosyl)ation, UV resistance, 3-aminobenzamide, mammalian cell lines
- MeSH terms
- Animals, Cell Line, Cell Survival, DNA, DNA Damage, DNA Repair, Endodeoxyribonucleases, Cricetinae, Humans, Hydroxyurea, Kinetics, Mammals, Recombinant Proteins, Transfection, Ultraviolet Rays, Xeroderma Pigmentosum, CHO Cells, Aphidicolin, Schizosaccharomyces pombe Proteins
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