title: Phosphorylation of histone H4 serine 1 during DNA damage requires casein kinase II in S. cerevisiae.
abstract: Distinct patterns of posttranslational histone modifications can regulate DNA-templated events such as mitosis, transcription, replication, apoptosis, and DNA damage, suggesting the presence of a "histone code" in these nuclear processes. Phosphorylation of histone H2A S129 at sites of DNA double-strand breaks (DSBs) has been implicated in damage repair in yeast. Here, we describe another phosphorylation event on serine 1 (S1) of histone H4; this event is also associated with MMS- or phleomycin-induced DSBs but not with UV-induced DNA damage. Chromatin-immunoprecipitation (ChIP) studies of an HO-endonuclease-inducible strain show that S1 phosphorylation is specifically enhanced 20- to 25-fold in nucleosomes proximal to the DSB. In addition, we show that casein kinase II (CK2) can phosphorylate H4 S1 in vitro and that null or temperature-sensitive CK2 yeast mutants are defective for induction of H4 S1 phosphorylation upon DNA damage in vivo. Furthermore, H4 S1 phosphorylation and CK2 play a role in DSB re-joining as indicated by a nonhomologous end-joining (NHEJ) plasmid assay. CK2 has been implicated in regulating a DNA-damage response; our data suggest that histone H4 S1 is one of its physiological substrates. These data suggest that this modification is a part of the DNA-repair histone code.
authors.affiliation: Department of Pathology, Johns Hopkins School of Medicine, Baltimore, Maryland 21210, USA.
authors.forename: Wang L
authors.initials: WL
authors.lastname: Cheung
authors.forename: Fiona B
authors.initials: FB
authors.lastname: Turner
authors.forename: Thanuja
authors.initials: T
authors.lastname: Krishnamoorthy
authors.forename: Branden
authors.initials: B
authors.lastname: Wolner
authors.forename: Sung-Hee
authors.initials: SH
authors.lastname: Ahn
authors.forename: Melissa
authors.initials: M
authors.lastname: Foley
authors.forename: Jean A
authors.initials: JA
authors.lastname: Dorsey
authors.forename: Craig L
authors.initials: CL
authors.lastname: Peterson
authors.forename: Shelley L
authors.initials: SL
authors.lastname: Berger
authors.forename: C David
authors.initials: CD
authors.lastname: Allis
mesh_terms: D015153:Blotting, Western; D047390:Casein Kinase II / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D004249:DNA Damage; D004260:DNA Repair / Q000502:physiology*; D006657:Histones / Q000378:metabolism*; D009707:Nucleosomes / Q000378:metabolism; D010766:Phosphorylation; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D012694:Serine / Q000378:metabolism*
chemical_list: D006657:Histones; D009707:Nucleosomes; D012694:Serine; D047390:Casein Kinase II