Phosphorylation of histone H4 serine 1 during DNA damage requires casein kinase II in S. cerevisiae.
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.
Cheung
Wang L
WL
Department of Pathology, Johns Hopkins School of Medicine, Baltimore, Maryland 21210, USA.
Turner
Fiona B
FB
Krishnamoorthy
Thanuja
T
Wolner
Branden
B
Ahn
Sung-Hee
SH
Foley
Melissa
M
Dorsey
Jean A
JA
Peterson
Craig L
CL
Berger
Shelley L
SL
Allis
C David
CD
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*
D006657:Histones; D009707:Nucleosomes; D012694:Serine; D047390:Casein Kinase II