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| Subject Categories: Genome Stability & Dynamics | Genomic & Computational Biology |
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| The EMBO Journal
(2005) 24, 3952–3962, doi:10.1038/sj.emboj.7600849 Published online 27 October 2005 |
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| Transcriptome analysis reveals cyclobutane pyrimidine dimers as a major source of UV-induced DNA breaks |
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| George A Garinis1, James R Mitchell1, Michael J Moorhouse2, Katsuhiro Hanada1, Harm de Waard1, Dimitri Vandeputte1, Judith Jans1, 5, Karl Brand1, Marcel Smid3, Peter J van der Spek2, Jan H J Hoeijmakers1, Roland Kanaar1, 4 and Gijsbertus T J van der Horst1 |
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1 Department of Cell Biology and Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands 2 Department of Bioinformatics, Erasmus University Medical Center, Rotterdam, The Netherlands 3 Department of Medical Oncology, Josephine Nefkens Institute, Erasmus University Medical Center, Rotterdam, The Netherlands 4 Department of Radiation Oncology, Erasmus University Medical Center, Rotterdam, The Netherlands To whom correspondence should be addressed Gijsbertus T J van der Horst, Department of Cell Biology and Genetics, Center for Biomedical Genetics, Erasmus University Medical Center, PO Box 1738, 3000 DR Rotterdam, The Netherlands. Tel.: +31 10 408 7455; Fax: +31 10 408 9468; E-mail: g.vanderhorst@erasmusmc.nl 5 Present address: Medical Genetic Center, Department of Molecular and Cell Biology, University of California at Berkeley, 125 Koshland Hall, Berkeley, CA, USA Received 9 June 2005; Accepted 30 September 2005; Published online 27 October 2005. |
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| Abstract |
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Photolyase transgenic mice have opened new avenues to improve our understanding of the cytotoxic effects of ultraviolet (UV) light on skin by providing a means to selectively remove either cyclobutane pyrimidine dimers (CPDs) or pyrimidine (6-4) pyrimidone photoproducts. Here, we have taken a genomics approach to delineate pathways through which CPDs might contribute to the harmful effects of UV exposure. We show that CPDs, rather than other DNA lesions or damaged macromolecules, comprise the principal mediator of the cellular transcriptional response to UV. The most prominent pathway induced by CPDs is that associated with DNA double-strand break (DSB) signalling and repair. Moreover, we show that CPDs provoke accumulation of  -H2AX, P53bp1 and Rad51 foci as well as an increase in the amount of DSBs, which coincides with accumulation of cells in S phase. Thus, conversion of unrepaired CPD lesions into DNA breaks during DNA replication may comprise one of the principal instigators of UV-mediated cytotoxicity. |
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| Keywords: DNA damage, functional genomics, photolyase, UV irradiation |
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Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated RESEARCHThe EMBO Journal Article (02 Sep 2002) Chromatin structure modulates DNA repair by photolyase in vivo The EMBO Journal Article (15 Apr 1997) |
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