Biotinylation of K12 in histone H4 decreases in response to DNA double-strand breaks in human JAr choriocarcinoma cells.
We tested the hypothesis that biotinylation of K12 in histone H4 plays a role in the cellular response to double-strand breaks (DSB) of DNA in human cells. DSB were caused by treating choriocarcinoma JAr cells with etoposide. Biotinylation of K12 in histone H4 decreased by 50% as early as 10-20 min after initiation of treatment with etoposide. Biotinylation returned to initial levels 30-40 min after the addition of etoposide to the medium. Temporal patterns of K12-biotinylation were similar for human lymphoma cells. Phosphorylation of S14 of histone H2B and poly(ADP-ribosylation) of glutamate residues on histone H2A are known markers of DSB in DNA; these modifications increased 10-40 min after alterations in K12-biotinylation occurred. Decreased biotinylation of K12 of histone H4 was specific for DSB but was not detectable in response to single-strand breaks or the formation of thymine dimers. Biotin-deficient choriocarcinoma cells exhibited a 40% decrease in rates of survival in response to etoposide compared with biotin-sufficient controls. These studies suggest that the lack of biotinylation of K12 in histone H4 is an early signaling event in response to DSB.
Kothapalli
Nagarama
N
Department of Biochemistry, University of Nebraska, Lincoln, NE, USA.
Sarath
Gautam
G
Zempleni
Janos
J
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D001710:Biotin / Q000378:metabolism*; D019921:Biotinylation; D002470:Cell Survival; D002822:Choriocarcinoma; D004247:DNA / Q000378:metabolism*; D004249:DNA Damage / Q000502:physiology*; D005047:Etoposide / Q000494:pharmacology; D006657:Histones / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D008239:Lysine / Q000378:metabolism; D010766:Phosphorylation; D011740:Pyrimidine Dimers / Q000378:metabolism; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
D000972:Antineoplastic Agents, Phytogenic; D006657:Histones; D011740:Pyrimidine Dimers; D012694:Serine; D005047:Etoposide; D001710:Biotin; D004247:DNA; D008239:Lysine