Histone H1 dephosphorylation is mediated through a radiation-induced signal transduction pathway dependent on ATM

Ionizing radiation is known to activate multiple signal transduction pathwa ys, but the targets of these pathways are poorly understood. Phosphorylatio n of histone Ill is thought to have a role in chromatin condensation/ decon densation, and we asked whether ionizing radiation (IR) would alter H1 phos phorylation. Our data demonstrate that low doses of IR result in a dramatic , but transient, dephosphorylation of H1 isoforms, The in vivo IR-induced d ephosphorylation 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 H 1 phosphatase activity. Both activities were affected by radiation-induced signals in an ATM dependent manner. Thus, the rapid IR-induced dephosphoryl ation of H1 involves a pathway including ATM and a wortmannin-sensitive ste p leading to both inhibition of cyclin-dependent kinase activities as well as activation of H1 phosphatase(s).