Transcriptional activation of DNA-dependent protein kinase catalytic subunit gene expression by oestrogen receptor-α

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Senad Medunjanin - , TUD Dresden University of Technology (Author)
  • Sönke Weinert - , TUD Dresden University of Technology (Author)
  • David Poitz - , Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus Dresden, TUD Dresden University of Technology (Author)
  • Alexander Schmeisser - , Otto von Guericke University Magdeburg (Author)
  • Ruth H. Strasser - , TUD Dresden University of Technology (Author)
  • Ruediger C. Braun-Dullaeus - , Otto von Guericke University Magdeburg (Author)

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 E2 receptor antagonist ICI 182,780, we demonstrate that ERα knockdown reduces E2-induced upregulation of DNA-PKcs expression and activity in breast carcinoma cells. E2-induced DNA-PK transactivation results in an increased ability of the cells to repair DNA DSB. This previously unknown mechanism of DNA-PK regulation sheds new light on tumour biology and reveals new possibilities for the prevention and therapy of E2-sensitive proliferative diseases.

Details

Original languageEnglish
Pages (from-to)208-213
Number of pages6
JournalEMBO reports
Volume11
Issue number3
Publication statusPublished - Mar 2010
Peer-reviewedYes

External IDs

PubMed 20111054
ORCID /0000-0001-7803-1972/work/142235113

Keywords

Sustainable Development Goals

ASJC Scopus subject areas