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First published online August 20, 2008

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XPC and DNA: an on-off affair

The nuclear protein XPC is the major sensor of DNA damage during global genome nucleotide excision repair (GG-NER). XPC marks sites of damage by binding to the complementary undamaged DNA strand, but how does it find such sites within the vast excess of undamaged DNA in the mammalian genome? Wim Vermeulen, Adriaan Houtsmuller and colleagues (p. 2850) investigate this question by analysing the dynamics of GFP-tagged XPC. The authors show that XPC – unlike other NER proteins – colocalises with chromatin even in the absence of inducers of DNA damage. Using FRAP, they show that the nuclear mobility of XPC is slower than that of other NER proteins; moreover, the mobility of XPC (but not of an XPC point mutant that is deficient is DNA binding) slows further when DNA is damaged. The authors therefore propose that XPC constantly associates with and dissociates from DNA, and that the binding time increases in the presence of damage. They go on to show that, in unchallenged cells, XPC shuttles between the nucleus and cytoplasm. When cells are irradiated with UV light, however, shuttling is impeded and the nuclear XPC concentration increases. These results clarify the mechanism of genome scanning by XPC, and describe a novel regulatory mechanism for GG-NER.

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

Deborah Hoogstraten, Steven Bergink, Jessica M. Y. Ng, Vincent H. M. Verbiest, Martijn S. Luijsterburg, Bart Geverts, Anja Raams, Christoffel Dinant, Jan H. J. Hoeijmakers, Wim Vermeulen, and Adriaan B. Houtsmuller
JCS 2008 121: 2850-2859. [Abstract] [Full Text]  

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JCS Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content Social Bookmarking                         What's this?