This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services 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 Dunn, J. Articles by Rünger, T. M. Search for Related Content PubMed PubMed Citation Articles by Dunn, J. Articles by Rünger, T. M.

Activation of the Fanconi Anemia/BRCA Pathway and Recombination Repair in the Cellular Response to Solar Ultraviolet Light

Department of Dermatology, Boston University School of Medicine, Boston, Massachusetts

Requests for reprints: Thomas M. Rünger, Department of Dermatology, Boston University School of Medicine, 609 Albany Street, Boston, MA 02118. Phone: 617-638-5551; Fax: 617-638-5515; E-mail: truenger{at}bu.edu.

Recombination repair plays an important role in the processing of DNA double-strand breaks (DSB) and DNA cross-links, and has been suggested to be mediated by the activation of the Fanconi anemia (FA)/BRCA pathway. Unlike DNA damage generated by ionizing radiation or DNA cross-linking, UV light–induced DNA damage is not commonly thought to require recombination for processing, as UV light does not directly induce DSBs or DNA cross-links. To elucidate the role of recombination repair in the cellular response to UV, we studied the FA/BRCA pathway in primary skin cells exposed to solar–simulated light. UV-induced monoubiquitination of the FANCD2 protein and formation of FANCD2 nuclear foci confirmed the activation of the pathway by UV light. This was only observed when cells were irradiated during S phase and was not caused by directly UV-induced DSBs. UV-exposed cells did not exhibit FANCD2 nuclear foci once they entered mitosis or when growth-arrested. In addition, UV-induced nuclear foci of the recombination proteins, RAD51 and BRCA1, colocalized with FANCD2 foci. We suggest that in response to UV light, when nucleotide excision repair failed to repair, or when translesional DNA synthesis failed to bypass UV-induced DNA photoproducts, the FA/BRCA pathway mediates the recombination repair of replication forks stalled at DNA photoproducts as a third line of defense. (Cancer Res 2006; 66(23): 11140-7)

This article has been cited by other articles:

				D. Kranz, C. Dohmesen, and M. Dobbelstein BRCA1 and Tip60 determine the cellular response to ultraviolet irradiation through distinct pathways J. Cell Biol., July 14, 2008; 182(1): 197 - 213. [Abstract] [Full Text] [PDF]

				X. Wang, R. D. Kennedy, K. Ray, P. Stuckert, T. Ellenberger, and A. D. D'Andrea Chk1-Mediated Phosphorylation of FANCE Is Required for the Fanconi Anemia/BRCA Pathway Mol. Cell. Biol., April 15, 2007; 27(8): 3098 - 3108. [Abstract] [Full Text] [PDF]