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Global Epigenetic Analysis Reveals H3K27 Methylation as a Mediator of Double Strand Break Repair

ABSTRACT: Ionizing Radiation is a ubiquitous cancer treatment modality which works in large part by inducing DNA Double Strand Breaks (DSBs). Recently, is has become apparent that chromatin surrounding DSBs is important for recognition of breaks, recruitment of repair factors, and timely DSB resolution. Here, we use tandem mass spectrometry proteomics to analyze global histone modification patterns in breast cancer cells after exposure to ionizing radiation. We find widespread and long-lasting changes to the epigenome. Specifically, we show that H3K27 trimethylation, a known regulator of cell fate and gene expression, increases after DNA damage. By microscopy, we show that these changes are rapid and occur proximate to sites of DNA damage. Lastly, using inhibitors of the H3K27 methyltransferase EZH2 we show that EZH2 is necessary for proper DNA damage recognition and survival of cells following IR exposure. Taken together, these results uncover suggest new, transcription-independent roles for epigenetic modifiers including EZH2 which could lead to novel chromatin biology.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Donald Wolfgeher

LAB HEAD: Stephen J. Kron

PROVIDER: PXD019388 | Pride | 2026-07-16

REPOSITORIES: Pride

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Dataset's files

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			Action	DRS
	191015_Histones_SwiSnf.fasta.fasta	Fasta
	191016_JL2_MQ_PhUb_SEARCH.zip	Other
	200117_JL2_Epiprofile.zip	Other
	20171110_MRM_Timecourse.zip	Other
	qe2_2018mar28_19_uc180308_jl2-06_TrypPr_0hr.raw	Raw

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