Drosophila p53 preserves genomic stability by regulating cell death.
When animal cells are exposed to stressful conditions, the tumor suppressor protein p53 restrains growth by promoting an arrested cell cycle or initiating a cell death program. How these distinct fates are specified through the action of a single protein is not known. To study its functions in vivo we produced a targeted mutation at the Drosophila p53 (Dmp53) locus. We show that Dmp53 is required for damage-induced apoptosis but not for cell-cycle arrest. Dmp53 function is also required for damage-induced transcription of two tightly linked cell death activators, reaper and sickle. When challenged by ionizing radiation, Dmp53 mutants exhibit radiosensitivity and genomic instability. Hence, elevated mutant loads were not caused by defective checkpoint functions but instead correlated with failures in p53-associated cell death. Our studies support the notion that core ancestral functions of the p53 gene family are intimately coupled to cell death as an adaptive response to maintain genomic stability.
Sogame
Naoko
N
Department of Cell Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9039, USA.
Kim
Misoo
M
Abrams
John M
JM
D000818:Animals; D030801:Animals, Genetically Modified; D017209:Apoptosis / Q000235:genetics*; D002453:Cell Cycle / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics; D004331:Drosophila melanogaster / Q000166:cytology* / Q000235:genetics* / Q000528:radiation effects; D018390:Gene Targeting; D017344:Genes, Insect; D016158:Genes, p53; D009154:Mutation; D011836:Radiation Tolerance / Q000235:genetics; D014158:Transcription, Genetic / Q000528:radiation effects
D029721:Drosophila Proteins; C086973:rpr protein, Drosophila