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

Hoogstraten, Deborah; Bergink, Steven; Verbiest, Vincent; Luijsterburg, Martijn S.; Geverts, Bart; Raams, Anja; Dinant, Christoffel; Hoeijmakers, Jan H.J.; Vermeulen, Wim; Houtsmuller, Adriaan B.

doi:10.1242/jcs.03502

Cited by 25 publications

(56 citation statements)

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“…The fusion proteins were expressed in human repair-deficient XP4PA-SV and XP2OS-SV cells, lacking functional XPC and XPA, respectively. Expression of the fusion proteins re-established UV resistance of the cell lines, showing that the EGFP-tagged NER proteins are functional (Hoogstraten et al, 2008;Rademakers et al, 2003). Moreover, the nuclear concentration of the fusion proteins was similar to that of the endogenous proteins in wild-type cells (Hoogstraten et al, 2008;Rademakers et al, 2003).…”

Section: Visualization Of Dna Damage and Ner Proteins By Fluorescencementioning

confidence: 79%

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Spatial organization of nucleotide excision repair proteins after UV-induced DNA damage in the human cell nucleus

Solimando

Luijsterburg

Vecchio

et al. 2009

Journal of Cell Science

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Nucleotide excision repair (NER) is an evolutionary conserved DNA repair system that is essential for the removal of UV-induced DNA damage. In this study we investigated how NER is compartmentalized in the interphase nucleus of human cells at the ultrastructural level by using electron microscopy in combination with immunogold labeling. We analyzed the role of two nuclear compartments: condensed chromatin domains and the perichromatin region. The latter contains transcriptionally active and partly decondensed chromatin at the surface of condensed chromatin domains. We studied the distribution of the damage-recognition protein XPC and of XPA, which is a central component of the chromatin-associated NER complex. Both XPC and XPA rapidly accumulate in the perichromatin region after UV irradiation, whereas only XPC is also moderately enriched in condensed chromatin domains. These observations suggest that DNA damage is detected by XPC throughout condensed chromatin domains, whereas DNA-repair complexes seem preferentially assembled in the perichromatin region. We propose that UV-damaged DNA inside condensed chromatin domains is relocated to the perichromatin region, similar to what has been shown for DNA replication. In support of this, we provide evidence that UV-damaged chromatin domains undergo expansion, which might facilitate the translocation process. Our results offer novel insight into the dynamic spatial organization of DNA repair in the human cell nucleus.

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Section: Visualization Of Dna Damage and Ner Proteins By Fluorescencementioning

confidence: 79%

“…To this aim, we generated cell lines stably expressing XPC-EGFP and EGFP-XPA (Hoogstraten et al, 2008;Rademakers et al, 2003). The fusion proteins were expressed in human repair-deficient XP4PA-SV and XP2OS-SV cells, lacking functional XPC and XPA, respectively.…”

Section: Visualization Of Dna Damage and Ner Proteins By Fluorescencementioning

confidence: 99%

Spatial organization of nucleotide excision repair proteins after UV-induced DNA damage in the human cell nucleus

Solimando

Luijsterburg

Vecchio

et al. 2009

Journal of Cell Science

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“…Erdel et al, 2011;Halford and Marko, 2004;Mueller et al, 2010;Mueller et al, 2008;Phair et al, 2004;Sprague and McNally, 2005;Sprague et al, 2004;van Royen et al, 2011). In a simple model, proteins diffuse freely though the nucleoplasm and find their targets by random collision, resulting in binding to specific and nonspecific binding sites (Gorski et al, 2006;Halford and Marko, 2004;Hoogstraten et al, 2008;Houtsmuller et al, 1999;McNally et al, 2000;Mueller et al, 2008). However, more sophisticated models based on in vitro experiments using isolated DNA suggest that proteins slide along the DNA strand (1D diffusion) or over the chromatin surface enabling proteins to bypass obstacles (2D diffusion) (Blainey et al, 2009;Gorman et al, 2007;Kampmann, 2004).…”

Section: Discussionmentioning

confidence: 99%

Androgen receptor complexes probe DNA for recognition sequences by short random interactions

Royen

Cappellen

Geverts

et al. 2014

Journal of Cell Science

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BSTRACTOwing to the tremendous progress in microscopic imaging of fluorescently labeled proteins in living cells, the insight into the highly dynamic behavior of transcription factors has rapidly increased over the past decade. However, a consistent quantitative scheme of their action is still lacking. Using the androgen receptor (AR) as a model system, we combined three different fluorescence microscopy assays: single-molecule microscopy, photobleaching and correlation spectroscopy, to provide a quantitative model of the action of this transcription factor. This approach enabled us to distinguish two types of AR-DNA binding: very brief interactions, in the order of a few hundred milliseconds, and hormone-induced longer-lasting interactions, with a characteristic binding time of several seconds. In addition, freely mobile ARs were slowed down in the presence of hormone, suggesting the formation of large AR-co-regulator complexes in the nucleoplasm upon hormone activation. Our data suggest a model in which mobile hormone-induced complexes of transcription factors and co-regulators probe DNA by briefly binding at random sites, only forming relatively stable transcription initiation complexes when bound to specific recognition sequences.

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“…Cells were incubated for 48 h under standard culture conditions and used to determine the intracellular localization or recruitment dynamics of the specified fluorescently tagged fusion protein. With the LN428 cell lines, an identical procedure (see above) was employed using a pEGFP-N3 vector that harbors full-length XPC (15).…”

Section: Methodsmentioning

confidence: 99%

NEIL1 Responds and Binds to Psoralen-induced DNA Interstrand Crosslinks

McNeill

Paramasivam

Baldwin

et al. 2013

Journal of Biological Chemistry

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Background: Components of base excision repair participate in the processing of psoralen-induced DNA adducts. Results: NEIL1 glycosylase responds and binds to psoralen interstrand crosslinks, and interferes with efficient recognition and removal of these lesions. Conclusion: NEIL1 exhibits affinity for DNA interstrand crosslinks and regulates crosslink processing. Significance: Besides the efficiency of the canonical pathways, the abundance and composition of NEIL1 may influence responsiveness to environmental and therapeutic DNA crosslinking agents.

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

Cited by 25 publications

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Spatial organization of nucleotide excision repair proteins after UV-induced DNA damage in the human cell nucleus

Spatial organization of nucleotide excision repair proteins after UV-induced DNA damage in the human cell nucleus

Androgen receptor complexes probe DNA for recognition sequences by short random interactions

NEIL1 Responds and Binds to Psoralen-induced DNA Interstrand Crosslinks

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