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DNA methylation changes following DNA damage in prostate cancer cells


Sutton, LP and Jeffreys, SA and Phillips, JL and Taberlay, PC and Holloway, AF and Ambrose, M and Joo, J-HE and Young, A and Berry, R and Skala, M and Brettingham-Moore, KH, DNA methylation changes following DNA damage in prostate cancer cells, Epigenetics, 14, (10) pp. 989-1002. ISSN 1559-2294 (2019) [Refereed Article]


Copyright Statement

Copyright 2019 The Authors. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)

DOI: doi:10.1080/15592294.2019.1629231


Many cancer therapies operate by inducing double-strand breaks (DSBs) in cancer cells, however treatment-resistant cells rapidly initiate mechanisms to repair damage enabling survival. While the DNA repair mechanisms responsible for cancer cell survival following DNA damaging treatments are becoming better understood, less is known about the role of the epigenome in this process. Using prostate cancer cell lines with differing sensitivities to radiation treatment, we analysed the DNA methylation profiles prior to and following a single dose of radiotherapy (RT) using the Illumina Infinium HumanMethylation450 BeadChip platform. DSB formation and repair, in the absence and presence of the DNA hypomethylating agent, 5-azacytidine (5-AzaC), were also investigated using γH2A.X immunofluorescence staining. Here we demonstrate that DNA methylation is generally stable following a single dose of RT; however, a small number of CpG sites are stably altered up to 14 d following exposure. While the radioresistant and radiosensitive cells displayed distinct basal DNA methylation profiles, their susceptibility to DNA damage appeared similar demonstrating that basal DNA methylation has a limited influence on DSB induction at the regions examined. Recovery from DSB induction was also similar between these cells. Treatment with 5-AzaC did not sensitize resistant cells to DNA damage, but rather delayed recruitment of phosphorylated BRCA1 (S1423) and repair of DSBs. These results highlight that stable epigenetic changes are possible following a single dose of RT and may have significant clinical implications for cancer treatment involving recurrent or fractionated dosing regimens.

Item Details

Item Type:Refereed Article
Keywords:prostate cancer, DNA damage, DNA repair, DNA methylation, epigenetics, radiotherapy, treatment response, radiation resistance
Research Division:Biomedical and Clinical Sciences
Research Group:Oncology and carcinogenesis
Research Field:Cancer cell biology
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Sutton, LP (Ms Laura Sutton)
UTAS Author:Jeffreys, SA (Miss Sarah Jeffreys)
UTAS Author:Phillips, JL (Dr Jessica Phillips)
UTAS Author:Taberlay, PC (Associate Professor Phillippa Taberlay)
UTAS Author:Holloway, AF (Professor Adele Holloway)
UTAS Author:Ambrose, M (Dr Mark Ambrose)
UTAS Author:Young, A (Miss Arabella Young)
UTAS Author:Berry, R (Ms Rachael Berry)
UTAS Author:Brettingham-Moore, KH (Dr Kate Brettingham-Moore)
ID Code:133257
Year Published:2019
Web of Science® Times Cited:12
Deposited By:Medicine
Deposited On:2019-06-19
Last Modified:2022-08-25
Downloads:29 View Download Statistics

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