Relative contribution of DNA repair, cell cycle checkpoints, and cell death to survival after DNA damage in Drosophila larvae.
BACKGROUND
Components of the DNA damage checkpoint are essential for surviving exposure to DNA damaging agents. Checkpoint activation leads to cell cycle arrest, DNA repair, and apoptosis in eukaryotes. Cell cycle regulation and DNA repair appear essential for unicellular systems to survive DNA damage. The relative importance of these responses and apoptosis for surviving DNA damage in multicellular organisms remains unclear.


RESULTS
After exposure to ionizing radiation, wild-type Drosophila larvae regulate the cell cycle and repair DNA; grp (DmChk1) mutants cannot regulate the cell cycle but repair DNA; okra (DmRAD54) mutants regulate the cell cycle but are deficient in repair of double strand breaks (DSB); mei-41 (DmATR) mutants cannot regulate the cell cycle and are deficient in DSB repair. All undergo radiation-induced apoptosis. p53 mutants regulate the cell cycle but fail to undergo apoptosis. Of these, mutants deficient in DNA repair, mei-41 and okra, show progressive degeneration of imaginal discs and die as pupae, while other genotypes survive to adulthood after irradiation. Survival is accompanied by compensatory growth of imaginal discs via increased nutritional uptake and cell proliferation, presumably to replace dead cells.


CONCLUSIONS
DNA repair is essential for surviving radiation as expected; surprisingly, cell cycle regulation and p53-dependent cell death are not. We propose that processes resembling regeneration of discs act to maintain tissues and ultimately determine survival after irradiation, thus distinguishing requirements between muticellular and unicellular eukaryotes.
Jaklevic
Burnley R
BR
MCD Biology, University of Colorado, Boulder, CO 80309, USA.
Su
Tin Tin
TT
D000818:Animals; D001921:Brain / Q000378:metabolism / Q000502:physiology*; D001973:Bromodeoxyuridine; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000235:genetics; D016923:Cell Death / Q000502:physiology*; D000071877:Checkpoint Kinase 1; D004249:DNA Damage / Q000528:radiation effects*; D004260:DNA Repair / Q000235:genetics / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics; D004331:Drosophila melanogaster; D004527:Egg Proteins / Q000235:genetics; D007150:Immunohistochemistry; D007814:Larva / Q000502:physiology; D008856:Microscopy, Fluorescence; D017346:Protein Serine-Threonine Kinases
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D004527:Egg Proteins; D000071877:Checkpoint Kinase 1; C444435:Mei-41 protein, Drosophila; D017346:Protein Serine-Threonine Kinases; C000605877:grp protein, Drosophila; D001973:Bromodeoxyuridine