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First published online 5 August 2008
doi: 10.1242/jcs.031708

This Article Figures Only Full Text Full Text (PDF) Supplementary Material A correction has been published A correction has been published All Versions of this Article: jcs.031708v1 121/17/2850    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hoogstraten, D. Articles by Houtsmuller, A. B. Search for Related Content PubMed PubMed Citation Articles by Hoogstraten, D. Articles by Houtsmuller, A. B. Social Bookmarking                         What's this?

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

¹ Department of Cell Biology and Genetics, Erasmus MC Rotterdam, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands
² Department of Pathology (Josephine Nefkens Institute), Erasmus MC Rotterdam, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands
³ Swammerdam Institute for Life Sciences, University of Amsterdam, Kruislaan 318, 1098 SM Amsterdam, The Netherlands

^* Authors for correspondence (e-mail: w.vermeulen{at}erasmusmc.nl; a.houtsmuller{at}erasmusmc.nl)

Accepted 3 June 2008

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.

Key words: DNA binding, DNA repair, Live cell reaction kinetics

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