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.