Phosphorylation of histone H4 serine 1 during DNA damage requires casein kinase II in S. cerevisiae
Biochemistry & Molecular Pharmacology
Graduate School of Biomedical Sciences; Program in Molecular Medicine
Medical Subject Headings
Blotting, Western; Casein Kinase II; Chromatin Immunoprecipitation; *DNA Damage; DNA Repair; Histones; Nucleosomes; Phosphorylation; Saccharomyces cerevisiae; Serine
Life Sciences | Medicine and Health Sciences
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.
Rights and Permissions
Citation: Curr Biol. 2005 Apr 12;15(7):656-60. Link to article on publisher's site
DOI of Published Version
Current biology : CB
Cheung, Wang L.; Turner, Fiona B.; Krishnamoorthy, Thanuja; Wolner, Branden; Ahn, Sung-Hee; Foley, Melissa Anne; Dorsey, Jean A.; Peterson, Craig L.; Berger, Shelley L.; and Allis, C. David, "Phosphorylation of histone H4 serine 1 during DNA damage requires casein kinase II in S. cerevisiae" (2005). GSBS Student Publications. 206.