Cited by 122DNA Repair MechanismsNuclear Structure and FunctionCarcinogens and Genotoxicity Assessment

Versatile DNA damage detection by the global genome nucleotide excision repair protein XPC

Open access
Hoogstraten, Deborah, Bergink, Steven, Ng, Jessica M. Y., Verbiest, Vincent H. M., Luijsterburg, Martijn S., Geverts, Bart, Raams, Anja, Dinant, Christoffel +3 more·2008·Journal of Cell Science

Abstract

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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Crossref · 10.1242/jcs.031708

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62 of 62 references verified0 citation errors · 0 not checkable

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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
Venue
Journal of Cell Science
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
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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