UV-DDB-dependent regulation of nucleotide excision repair kinetics in living cells
Abstract
Although the basic principle of nucleotide excision repair (NER), which can eliminate various DNA lesions, have been dissected at the genetic, biochemical and cellular levels, the important in vivo regulation of the critical damage recognition step is poorly understood. Here we analyze the in vivo dynamics of the essential NER damage recognition factor XPC fused to the green fluorescence protein (GFP). Fluorescence recovery after photobleaching analysis revealed that the UV-induced transient immobilization of XPC, reflecting its actual engagement in NER, is regulated in a biphasic manner depending on the number of (6-4) photoproducts and titrated by the number of functional UV-DDB molecules. A similar biphasic UV-induced immobilization of TFIIH was observed using XPB-GFP. Surprisingly, subsequent integration of XPA into the NER complex appears to follow only the low UV dose immobilization of XPC. Our results indicate that when only a small number of (6-4) photoproducts are generated, the UV-DDB-dependent damage recognition pathway predominates over direct recognition by XPC, and they also suggest the presence of rate-limiting regulatory steps in NER prior to the assembly of XPA.
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DDB2 and XPC have inherent recognition capacity for UVR-induced DNA damage and instigate prompt formation of pre-incision complex at damage sites.
“DDB2 and XPC have the inherent recognition capacity for UVR-induced DNA damage, and instigate the prompt formation of pre-incision complex at the damage sites [5;57–59].”
From ATR- and ATM-Mediated DNA Damage Response Is Dependent on Excision Repair Assembly during G1 but Not in S Phase of Cell Cycle (2016) · cites this paper as [57]
DDB2 and XPC recruitment can be immuno-detected at damage sites by ~5 minutes post-irradiation.
“DDB2 and XPC recruitment can be immuno-detected at the damage sites by ~5 minutes post-irradiation [57;60].”
From ATR- and ATM-Mediated DNA Damage Response Is Dependent on Excision Repair Assembly during G1 but Not in S Phase of Cell Cycle (2016) · cites this paper as [57]
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References 77 · Cited by 76
- Authors
- Nishi, R., Alekseev, S., Dinant, C., Hoogstraten, D., Houtsmuller, A. B., Hoeijmakers, J. H. J., Vermeulen, W., Hanaoka, F., & Sugasawa, K.
- Affiliations
- Japan Science and Technology Agency (JP)
- Erasmus MC (NL)
- Corresponding author
- Sugasawa, Kaoru
- ORCID
- Venue
- DNA Repair
- Publisher
- Elsevier BV
- Published
- 2009-06
- Volume
- 8
- Issue
- 6
- Pages
- 767-776
- ISSN
- 1568-7856 (ISSN-L)
- 1568-7864
- OpenAlex
- W2083159605
- Cited by
- 76
- References
- 77
- Citations by year
- 2025: 2 · 2022: 2 · 2021: 3 · 2020: 3 · 2019: 8 · 2018: 6 · 2017: 6 · 2016: 6 · 2015: 5 · 2014: 2 · 2013: 3 · 2012: 5
- FWCI
- 3.87
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- DNA repair (publishedVersion)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- Funders
- Japan Science and Technology Agency
- RIKEN
- Ministry of Education, Culture, Sports, Science and Technology
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Keywords
- nucleotide excision repair, XPC, XPA, TFIIH, XPB, 6-4 photoproducts, damage detection, FRAP, repair kinetics
- MeSH terms
- Cells, Cultured, DNA Damage, DNA Repair, DNA-Binding Proteins, Fibroblasts, Humans, Immunoenzyme Techniques, Kinetics, Ultraviolet Rays, RNA, Small Interfering, Green Fluorescent Proteins, Transcription Factor TFIIH, Xeroderma Pigmentosum Group A Protein, DNA Breaks, Double-Stranded
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