Depletion of Histone Demethylase Jarid1A Resulting in Histone Hyperacetylation and Radiation Sensitivity Does Not Affect DNA Double-Strand Break Repair
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Depletion of Histone Demethylase Jarid1A Resulting in Histone Hyperacetylation and Radiation Sensitivity Does Not Affect DNA Double-Strand Break Repair. / Penterling, Corina; Drexler, Guido A; Böhland, Claudia; Stamp, Ramona; Wilke, Christina; Braselmann, Herbert; Caldwell, Randolph B; Reindl, Judith; Girst, Stefanie; Greubel, Christoph; Siebenwirth, Christian; Mansour Khalfallah, Wael Yassin; Borgmann, Kerstin; Dollinger, Günther; Unger, Kristian; Friedl, Anna A.
In: PLOS ONE, Vol. 11, No. 6, 2016, p. e0156599.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Depletion of Histone Demethylase Jarid1A Resulting in Histone Hyperacetylation and Radiation Sensitivity Does Not Affect DNA Double-Strand Break Repair
AU - Penterling, Corina
AU - Drexler, Guido A
AU - Böhland, Claudia
AU - Stamp, Ramona
AU - Wilke, Christina
AU - Braselmann, Herbert
AU - Caldwell, Randolph B
AU - Reindl, Judith
AU - Girst, Stefanie
AU - Greubel, Christoph
AU - Siebenwirth, Christian
AU - Mansour Khalfallah, Wael Yassin
AU - Borgmann, Kerstin
AU - Dollinger, Günther
AU - Unger, Kristian
AU - Friedl, Anna A
PY - 2016
Y1 - 2016
N2 - 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.
AB - 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.
KW - Journal Article
U2 - 10.1371/journal.pone.0156599
DO - 10.1371/journal.pone.0156599
M3 - SCORING: Journal article
C2 - 27253695
VL - 11
SP - e0156599
JO - PLOS ONE
JF - PLOS ONE
SN - 1932-6203
IS - 6
ER -
