γ-H2AX and other histone post-translational modifications in the clinic

Christophe E. Redon, Sossou Weyemi, Palak R. Parekh, Dejun Huang, Allison S. Burrell, William M. Bonner

Research output: Contribution to journalArticle

Abstract

Chromatin is a dynamic complex of DNA and proteins that regulates the flow of information from genome to end product. The efficient recognition and faithful repair of DNA damage, particularly double-strand damage, is essential for genomic stability and cellular homeostasis. Imperfect repair of DNA double-strand breaks (DSBs) can lead to oncogenesis. The efficient repair of DSBs relies in part on the rapid formation of foci of phosphorylated histone H2AX (γ-H2AX) at each break site, and the subsequent recruitment of repair factors. These foci can be visualized with appropriate antibodies, enabling low levels of DSB damage to be measured in samples obtained from patients. Such measurements are proving useful to optimize treatments involving ionizing radiation, to assay . in vivo the efficiency of various drugs to induce DNA damage, and to help diagnose patients with a variety of syndromes involving elevated levels of γ-H2AX. We will survey the state of the art of utilizing γ-H2AX in clinical settings. We will also discuss possibilities with other histone post-translational modifications. The ability to measure . in vivo the responses of individual patients to particular drugs and/or radiation may help optimize treatments and improve patient care. This article is part of a Special Issue entitled: Chromatin in time and space.

Original languageEnglish (US)
Pages (from-to)743-756
Number of pages14
JournalBiochimica et Biophysica Acta - Gene Regulatory Mechanisms
Volume1819
Issue number7
DOIs
StatePublished - Jul 2012
Externally publishedYes

Fingerprint

Post Translational Protein Processing
Histones
Repair
DNA Damage
Chromatin
DNA
Double-Stranded DNA Breaks
Genomic Instability
Ionizing Radiation
Pharmaceutical Preparations
Ionizing radiation
Patient Care
Carcinogenesis
Homeostasis
Genome
Radiation
Assays
Antibodies
Genes
Therapeutics

Keywords

  • γ-H2AX focus
  • Biodosimeter
  • Chemotherapy
  • Clinical study
  • DNA double-strand break
  • Ionizing radiation

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Genetics
  • Molecular Biology
  • Structural Biology

Cite this

γ-H2AX and other histone post-translational modifications in the clinic. / Redon, Christophe E.; Weyemi, Sossou; Parekh, Palak R.; Huang, Dejun; Burrell, Allison S.; Bonner, William M.

In: Biochimica et Biophysica Acta - Gene Regulatory Mechanisms, Vol. 1819, No. 7, 07.2012, p. 743-756.

Research output: Contribution to journalArticle

Redon, Christophe E. ; Weyemi, Sossou ; Parekh, Palak R. ; Huang, Dejun ; Burrell, Allison S. ; Bonner, William M. / γ-H2AX and other histone post-translational modifications in the clinic. In: Biochimica et Biophysica Acta - Gene Regulatory Mechanisms. 2012 ; Vol. 1819, No. 7. pp. 743-756.
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