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

Research output: Contribution to journalArticleResearchpeer-review

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 μM, 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.

Original languageEnglish
Pages (from-to)3963-3971
Number of pages9
JournalOncogene
Volume26
Issue number27
DOIs
Publication statusPublished - 7 Jun 2007
Externally publishedYes

Keywords

  • γH2AX
  • ChIP
  • HDAC inhibitor
  • Histone acetylation
  • Radiation sensitivity
  • Trichostatin A

Cite this

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title = "Disparity of histone deacetylase inhibition on repair of radiation-induced DNA damage on euchromatin and constitutive heterochromatin compartments",
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 μM, 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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author = "Karagiannis, {T. C.} and H. Kn and A. El-Osta",
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Disparity of histone deacetylase inhibition on repair of radiation-induced DNA damage on euchromatin and constitutive heterochromatin compartments. / Karagiannis, T. C.; Kn, H.; El-Osta, A.

In: Oncogene, Vol. 26, No. 27, 07.06.2007, p. 3963-3971.

Research output: Contribution to journalArticleResearchpeer-review

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