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Penterling, C.* ; Drexler, G.A.* ; Böhland, C.* ; Stamp, R.* ; Wilke, C. ; Braselmann, H. ; Caldwell, R.B. ; Reindl, J.* ; Girst, S.* ; Greubel, C.* ; Siebenwirth, C.* ; Mansour, W.Y.* ; Borgmann, K.* ; Dollinger, G.* ; Unger, K. ; Friedl, A.A.

Depletion of histone demethylase Jarid1A resulting in histone hyperacetylation and radiation sensitivity does not affect DNA double-strand break repair.

PLoS ONE 11:e0156599 (2016)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Histone demethylases have recently gained interest as potential targets in cancer treatment and several histone demethylases have been implicated in the DNA damage response. We investigated the effects of siRNA-mediated depletion of histone demethylase Jarid1A (KDM5A, RBP2), which demethylates transcription activating tri- and dimethylated lysine 4 at histone H3 (H3K4me3/me2), on growth characteristics and cellular response to radiation in several cancer cell lines. In unirradiated cells Jarid1A depletion lead to histone hyperacetylation while not affecting cell growth. In irradiated cells, depletion of Jarid1A significantly increased cellular radiosensitivity. Unexpectedly, the hyperacetylation phenotype did not lead to disturbed accumulation of DNA damage response and repair factors 53BP1, BRCA1, or Rad51 at damage sites, nor did it influence resolution of radiation-induced foci or rejoining of reporter constructs. We conclude that the radiation sensitivity observed following depletion of Jarid1A is not caused by a deficiency in repair of DNA double-strand breaks.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Damage Response Protein; Deacetylase Inhibitors; Chromatin Compaction; Valproic Acid; Cancer-cells; Oncometabolite 2-hydroxyglutarate; Transcriptional Repression; Lysine Demethylases; H3k4 Demethylase; Gastric-cancer
ISSN (print) / ISBN 1932-6203
Journal PLoS ONE
Quellenangaben Volume: 11, Issue: 6, Pages: , Article Number: e0156599 Supplement: ,
Publisher Public Library of Science (PLoS)
Publishing Place Lawrence, Kan.
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) CCG Personalized Radiotherapy in Head and Neck Cancer (KKG-KRT)
Research Unit Radiation Cytogenetics (ZYTO)