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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)
Verlagsversion Forschungsdaten 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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter 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
Zeitschrift PLoS ONE
Quellenangaben Band: 11, Heft: 6, Seiten: , Artikelnummer: e0156599 Supplement: ,
Verlag Public Library of Science (PLoS)
Verlagsort Lawrence, Kan.
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) CCG Personalized Radiotherapy in Head and Neck Cancer (KKG-KRT)
Research Unit Radiation Cytogenetics (ZYTO)