De. Hallahan et al., C-JUN AND EGR-1 PARTICIPATE IN DNA-SYNTHESIS AND CELL-SURVIVAL IN RESPONSE TO IONIZING-RADIATION EXPOSURE, The Journal of biological chemistry, 270(51), 1995, pp. 30303-30309
Exposure of mammalian cells to ionizing radiation results in the induc
tion of the immediate early genes, c-jun and Egr-1, which encode trans
cription factors implicated in cell growth as well as the cellular res
ponse to oxidative stress, We studied the role of these immediate earl
y genes in cell cycle kinetics and cell survival following x-irradiati
on of clones containing inducible dominant negatives to c-jun and Egr-
1, The dominant negative constructs to c-jun (Delta 9) and Egr-1 (WT/E
gr) prevented x-ray induction of transcription through the AP-1 and Eg
r binding sites, respectively. Twenty percent of confluent, serum-depr
ived SQ20B human tumor cells, normal fibroblasts, and fibroblasts from
patients with ataxia telangiectasia entered S phase within 5 h of irr
adiation, Clones containing inducible Delta 9 and WT/Egr dominant nega
tive constructs demonstrated attenuation of the percentage of cells ex
iting G(1) phase and reduced survival following irradiation, These dat
a indicate that the dominant negatives to the stress-inducible immedia
te early genes Egr-1 and c-jun prevent the onset of S phase and reduce
the survival of human cells exposed to ionizing radiation.