Biotinylation of K12 in histone H4 decreases in response to DNA double-strand breaks in human JAr choriocarcinoma cells

J Nutr. 2005 Oct;135(10):2337-42. doi: 10.1093/jn/135.10.2337.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology
  • Biotin / metabolism*
  • Biotinylation
  • Cell Survival
  • Choriocarcinoma*
  • DNA / metabolism*
  • DNA Damage / physiology*
  • Etoposide / pharmacology
  • Histones / metabolism*
  • Humans
  • Jurkat Cells
  • Lysine / metabolism
  • Phosphorylation
  • Pyrimidine Dimers / metabolism
  • Serine / metabolism
  • Signal Transduction / physiology


  • Antineoplastic Agents, Phytogenic
  • Histones
  • Pyrimidine Dimers
  • Serine
  • Etoposide
  • Biotin
  • DNA
  • Lysine