Versatile DNA damage detection by the global genome nucleotide excision repair protein XPC
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To investigate how the nucleotide excision repair initiator XPC locates DNA damage in mammalian cell nuclei we analyzed the dynamics of GFP-tagged XPC. Photobleaching experiments showed that XPC constantly associates with and dissociates from chromatin in the absence of DNA damage. DNA-damaging agents retard the mobility of XPC, and UV damage has the most pronounced effect on the mobility of XPC-GFP. XPC exhibited a surprising distinct dynamic behavior and subnuclear distribution compared with other NER factors. Moreover, we uncovered a novel regulatory mechanism for XPC. Under unchallenged conditions, XPC is continuously exported from and imported into the nucleus, which is impeded when NER lesions are present. XPC is omnipresent in the nucleus, allowing a quick response to genotoxic stress. To avoid excessive DNA probing by the low specificity of the protein, the steady-state level in the nucleus is controlled by nucleus-cytoplasm shuttling, allowing temporally higher concentrations of XPC in the nucleus under genotoxic stress conditions.
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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 [59]
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- Authors
- Hoogstraten, D., Bergink, S., Ng, J. M. Y., Verbiest, V. H. M., Luijsterburg, M. S., Geverts, B., Raams, A., Dinant, C., Hoeijmakers, J. H. J., Vermeulen, W., & Houtsmuller, A. B.
- Affiliations
- Erasmus MC (NL)
- University of Amsterdam (NL)
- Corresponding author
- Vermeulen, Wim
- ORCID
- Venue
- Journal of Cell Science
- Publisher
- The Company of Biologists
- Published
- 2008-09-01
- Volume
- 121
- Issue
- 17
- Pages
- 2850-2859
- ISSN
- 0021-9533 (ISSN-L)
- 1477-9137
- OpenAlex
- W2152645308
- Cited by
- 122
- References
- 63
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 3 · 2023: 8 · 2022: 3 · 2021: 6 · 2020: 5 · 2019: 8 · 2018: 3 · 2017: 6 · 2016: 8 · 2015: 6 · 2014: 13 · 2013: 7 · 2012: 10
- FWCI
- 4.37
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- other-oa
- Locations
- Journal of Cell Science (publishedVersion)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
- UvA-DARE (University of Amsterdam) (submittedVersion)
- RePub (Erasmus University Rotterdam) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- 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 › Cancer Research › Carcinogens and Genotoxicity Assessment
- Keywords
- XPC, nucleotide excision repair, DNA damage detection, chromatin binding, UV-induced DNA damage, protein mobility, genotoxic stress response
- MeSH terms
- Amino Acid Sequence, Cell Line, Cell Nucleus, Cell Survival, DNA Damage, DNA Repair, DNA-Binding Proteins, Fibroblasts, Humans, Kinetics, Models, Biological, Molecular Sequence Data, Protein Binding, Recombinant Fusion Proteins, Ultraviolet Rays, Genome, Protein Transport, Fluorescence Recovery After Photobleaching, Green Fluorescent Proteins, Mutant Proteins, Transcription Factor TFIIH, Xeroderma Pigmentosum Group A Protein
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