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Disparity of histone deacetylase inhibition on repair of radiation-induced DNA damage on euchromatin and constitutive heterochromatin compartments

Oncogene volume 26, pages 3963–3971 (2007)Cite this article

A Corrigendum to this article was published on 26 July 2007

Abstract

Epigenetic regulation of chromatin structure is central to the process of DNA repair. A well-characterized epigenetic feature is the dynamic phosphorylation of the histone H2AX (γH2AX) and mobilization of double strand break (DSB) recognition and repair factors to the site. How chromatin structure is altered in response to DNA damage and how such alterations influence DSB repair mechanisms are currently relevant issues. Despite the clear link between histone deacetylases (HDACs) and radiosensitivity, how histone hyperacetylation influence DSB repair remains poorly understood. We have determined the structure of chromatin is a major factor determining radiosensitivity and repair in human cells. Trichostatin A (TSA) enhances radiosensitivity with dose modification factors of 1.2 and 1.9 at 0.2 and 1 μ M, respectively. Cells treated with TSA causing hyperacetylation and remodelling on euchromatic alleles coexist with γH2AX accumulation in radiosensitized cells. Formation of γH2AX on heterochromatin was significantly reduced even when cells were treated with TSA, suggesting that chromatin structure and histone hyperacetylation are pronounced features of radiation sensitivity and repair in euchromatic regions.

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Acknowledgements

We thank Dr Jun Okabe for his suggestions. The support of the Australian Institute of Nuclear Science and Engineering is acknowledged. TCK was the recipient of AINSE awards. Molecular Radiation Biology and Epigenetics in Human Health and Disease Laboratories are supported by the National Health and Medical Research Council of Australia (350359 and 268905). Dr El-Osta acknowledges the Conquer Fragile X Foundation, Lyonel and Joanna Middows Foundation and the Hazel & Pip Appel Charitable Trust.

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  1. T C Karagiannis and H Kn: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Molecular Radiation Biology, Trescowthick Research Laboratories, Peter MacCallum Cancer Centre, East Melbourne, Australia

    T C Karagiannis

  2. Department of Pathology, The University of Melbourne, Parkville, Australia

    T C Karagiannis

  3. Epigenetics in Human Health and Disease, Baker Medical Research Institute, The Alfred Medical Research and Education Precinct, Melbourne, Victoria, Australia

    H Kn & A El-Osta

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  1. T C Karagiannis
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Correspondence to A El-Osta.

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Karagiannis, T., Kn, H. & El-Osta, A. Disparity of histone deacetylase inhibition on repair of radiation-induced DNA damage on euchromatin and constitutive heterochromatin compartments. Oncogene 26, 3963–3971 (2007). https://doi.org/10.1038/sj.onc.1210174

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