title: Phosphorylation of histone H2B at DNA double-strand breaks.
abstract: Posttranslational modifications of histone tails regulate numerous biological processes including transcription, DNA repair, and apoptosis. Although recent studies suggest that structural alterations in chromatin are critical for triggering the DNA damage response, very little is known about the nature of DNA damage-induced chromatin perturbations. Here we show that the serine 14 residue in the NH(2)-terminal tail of histone H2B is rapidly phosphorylated at sites of DNA double-strand breaks. At late time points after irradiation, the phosphorylated form of H2B, H2B-(Ser14P), accumulates into irradiation-induced foci. H2B-(Ser14P) foci formation is not associated with the apoptotic phosphorylation of H2B but is strictly dependent on the phosphorylated isoform of H2AX. Our results broaden the spectrum of histone modifications that constitute the DNA damage "histone code" and suggest a model for the underlying chromatin structure within damage-induced foci.
authors.affiliation: Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Oscar
authors.initials: O
authors.lastname: Fernandez-Capetillo
authors.forename: C David
authors.initials: CD
authors.lastname: Allis
authors.forename: André
authors.initials: A
authors.lastname: Nussenzweig
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D002843:Chromatin / Q000502:physiology; D004249:DNA Damage / Q000502:physiology*; D004260:DNA Repair; D004307:Dose-Response Relationship, Radiation; D004622:Embryo, Mammalian; D005347:Fibroblasts / Q000166:cytology / Q000276:immunology / Q000528:radiation effects; D017930:Genes, Reporter; D006657:Histones / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D007259:Infrared Rays; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D016297:Mutagenesis, Site-Directed; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D002843:Chromatin; D006657:Histones