Maintenance of imaginal disc plasticity and regenerative potential in Drosophila by p53.
Following irradiation (IR), the DNA damage response (DDR) activates p53, which triggers death of cells in which repair cannot be completed. Lost tissue is then replaced and re-patterned through regeneration. We have examined the role of p53 in co-regulation of the DDR and tissue regeneration following IR damage in Drosophila. We find that after IR, p53 is required for imaginal disc cells to repair DNA, and in its absence the damage marker, γ-H2AX is persistently expressed. p53 is also required for the compensatory proliferation and re-patterning of the damaged discs, and our results indicate that cell death is not required to trigger these processes. We identify an IR-induced delay in developmental patterning in wing discs that accompanies an animal-wide delay of the juvenile-adult transition, and demonstrate that both of these delays require p53. In p53 mutants, the lack of developmental delays and of damage resolution leads to anueploidy and tissue defects, and ultimately to morphological abnormalities and adult inviability. We propose that p53 maintains plasticity of imaginal discs by co-regulating the maintenance of genome integrity and disc regeneration, and coordinating these processes with the physiology of the animal. These findings place p53 in a role as master coordinator of DNA and tissue repair following IR.
Department of Genetics & Development, Columbia University Medical Center, New York, NY 10032, USA.
Brent S
BS
Wells
Laura A
LA
Johnston
D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D002454:Cell Differentiation / Q000528:radiation effects; D049109:Cell Proliferation / Q000528:radiation effects; D004249:DNA Damage; D004260:DNA Repair / Q000528:radiation effects; D004331:Drosophila melanogaster / Q000166:cytology / Q000254:growth & development* / Q000502:physiology* / Q000528:radiation effects; D060227:Imaginal Discs / Q000166:cytology / Q000254:growth & development* / Q000502:physiology* / Q000528:radiation effects; D009154:Mutation / Q000235:genetics; D038081:Organogenesis / Q000528:radiation effects; D011679:Pupa / Q000254:growth & development / Q000528:radiation effects; D011839:Radiation, Ionizing; D012038:Regeneration / Q000528:radiation effects; D016019:Survival Analysis; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D014921:Wings, Animal / Q000166:cytology / Q000254:growth & development / Q000528:radiation effects; D014945:Wound Healing / Q000528:radiation effects
D016159:Tumor Suppressor Protein p53