Transcriptonal activation of DNA.doc

Transcriptional activation of DNA-dependent protein kinase catalytic subunit gene expression by oestrogen receptor-α Senad Medunjanin,1 S?nke Weinert,1 David Poitz,1 Alexander Schmeisser,2 Ruth H Strasser,1 and Ruediger C Braun-Dullaeusa,2 1Division of Cardiology, Department of Internal Medicine, Dresden University of Technology, Fetscherstrasse 74, 01307 Dresden, Germany 2Division of Cardiology, Department of Internal Medicine, Angiology and Pneumology, Magdeburg University, Leipziger Strasse 44, 39120 Magdeburg, Germany aTel: +49 391 6713203; Fax: +49 391 6713202; E-mail: ed.ugvo.dem@sueallud-nuarb.r Author information ? Article notes ? Copyright and License information ? Received June 12, 2009; Revised December 1, 2009; Accepted December 4, 2009. Copyright ? 2010, European Molecular Biology Organization This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits distribution, and reproduction in any medium, provided the original author and source are credited. This license does not permit commercial exploitation or the creation of derivative works without specific permission. This article has been cited by other articles in PMC. Go to: Abstract The cellular response to DNA double-strand break (DSB) occurs through an integrated sensing and signalling network that maintains genomic stability. Oestrogen (E2), among its many functions, is known to have a positive effect on global genomic DNA repair; however, the mechanism by which it functions is unclear. A central enzyme involved in DNA DSB repair in mammalian cells is the DNA-dependent protein kinase (DNA-PK). Here, we show that E2 enhances DNA-PK catalytic subunit (DNA-PKcs) promoter activity with subsequent transcriptional and translational upregulation of DNA-PKcs in a breast cancer cell line. We identify two potential E2 receptor-α (ERα)-binding sites in a region upstream from the DNA-PKcs initiation site. By using small interfering RNA and the specific