DNA double-strand break-induced phosphorylation of Drosophila histone variant H2Av helps prevent radiation-induced apoptosis

Nucleic Acids Res. 2002 Sep 1;30(17):3698-705. doi: 10.1093/nar/gkf496.


The response of eukaryotic cells to the formation of a double-strand break (DSB) in chromosomal DNA is highly conserved. One of the earliest responses to DSB formation is phosphorylation of the C-terminal tail of H2A histones located in nucleosomes near the break. Histone variant H2AX and core histone H2A are phosphorylated in mammals and budding yeast, respectively. We demonstrate the DSB-induced phosphorylation of histone variant H2Av in Drosophila melanogaster. H2Av is a member of the H2AZ family of histone variants. Ser137 within an SQ motif located near the C- terminus of H2Av was phosphorylated in response to gamma-irradiation in both tissue culture cells and larvae. Phosphorylation was detected within 1 min of irradiation and detectable after only 0.3 Gy of radiation exposure. Photochemically induced DSBs, but not general oxidative damage or UV-induced nicking of DNA, caused H2Av phosphorylation, suggesting that phosphorylation is DSB specific. Imaginal disc cells from Drosophila expressing a mutant allele of H2Av with its C-terminal tail deleted, and therefore unable to be phosphorylated, were more sensitive to radiation-induced apoptosis than were wildtype controls, suggesting that phosphorylation of H2Av is important for repair of radiation-induced DSBs. These observations suggest that in addition to providing the function of an H2AZ histone, H2Av is also the functional homolog in Drosophila of H2AX.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Apoptosis / genetics
  • Apoptosis / radiation effects*
  • Blotting, Western
  • Cell Line
  • DNA / genetics
  • DNA / metabolism
  • DNA Damage*
  • DNA Repair
  • Drosophila / genetics*
  • Drosophila / metabolism
  • Drosophila / radiation effects
  • Genotype
  • Histones / genetics
  • Histones / metabolism*
  • Larva / cytology
  • Larva / genetics
  • Larva / radiation effects
  • Molecular Sequence Data
  • Mutation
  • Phosphorylation
  • Sequence Homology, Amino Acid


  • Histones
  • DNA