title: γ-H2AX and other histone post-translational modifications in the clinic.
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.
authors.affiliation: Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, 9000 Rockville Pike, Bethesda, MD, 20892, USA.
authors.forename: Christophe E
authors.initials: CE
authors.lastname: Redon
authors.forename: Urbain
authors.initials: U
authors.lastname: Weyemi
authors.forename: Palak R
authors.initials: PR
authors.lastname: Parekh
authors.forename: Dejun
authors.initials: D
authors.lastname: Huang
authors.forename: Allison S
authors.initials: AS
authors.lastname: Burrell
authors.forename: William M
authors.initials: WM
authors.lastname: Bonner
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D002843:Chromatin / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded; D004307:Dose-Response Relationship, Radiation; D006657:Histones / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000628:therapy; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D002843:Chromatin; C468783:H2AX protein, human; D006657:Histones