title: Histone H1 dephosphorylation is mediated through a radiation-induced signal transduction pathway dependent on ATM.
abstract: Ionizing radiation is known to activate multiple signal transduction pathways, but the targets of these pathways are poorly understood. Phosphorylation of histone H1 is thought to have a role in chromatin condensation/decondensation, and we asked whether ionizing radiation (IR) would alter H1 phosphorylation. Our data demonstrate that low doses of IR result in a dramatic, but transient, dephosphorylation of H1 isoforms. The in vivo IR-induced dephosphorylation of H1 is completely blocked by wortmannin and is abrogated in ataxia telangiectasia cells. Furthermore, we measured radiation-induced inhibition of cyclin dependent kinase activity and activation of histone H1 phosphatase activity. Both activities were affected by radiation-induced signals in an ATM-dependent manner. Thus, the rapid IR-induced dephosphorylation of H1 involves a pathway including ATM and a wortmannin-sensitive step leading to both inhibition of cyclin-dependent kinase activities as well as activation of H1 phosphatase(s).
authors.affiliation: Department of Radiation Oncology, University of Virginia Health Science System, Charlottesville, Virginia 22908, USA.
authors.forename: C Y
authors.initials: CY
authors.lastname: Guo
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: D L
authors.initials: DL
authors.lastname: Brautigan
authors.forename: J M
authors.initials: JM
authors.lastname: Larner
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins; D002478:Cells, Cultured; D004249:DNA Damage; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism / Q000528:radiation effects; D006657:Histones / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D016350:Leucine Zippers; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases; D011506:Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000528:radiation effects*; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D006657:Histones; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011506:Proteins; D025521:Tumor Suppressor Proteins; D000077191:Wortmannin; C576324:ATM protein, human