Dmp53 protects the Drosophila retina during a developmentally regulated DNA damage response.
Ultraviolet (UV) light is absorbed by cellular proteins and DNA, promoting skin damage, aging and cancer. In this paper, we explore the UV response by cells of the Drosophila retina. We demonstrate that the retina enters a period of heightened UV sensitivity in the young developing pupa, a stage closely associated with its period of normal developmental programmed cell death. Injury to irradiated cells included morphology changes and apoptotic cell death; these defects could be completely accounted for by DNA damage. Cell death, but not morphological changes, was blocked by the caspase inhibitor P35. Utilizing genetic and microarray data, we provide evidence for the central role of Hid expression and for Diap1 protein stability in controlling the UV response. In contrast, we found that Reaper had no effect on UV sensitivity. Surprisingly, Dmp53 is required to protect cells from UV-mediated cell death, an effect attributed to its role in DNA repair. These in vivo results demonstrate that the cellular effects of DNA damage depend on the developmental status of the tissue.
Jassim
Omar W
OW
Department of Molecular Biology and Pharmacology, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8103, Saint Louis, MO 63110, USA.
Fink
Jill L
JL
Cagan
Ross L
RL
D000818:Animals; D017209:Apoptosis; D004249:DNA Damage; D029721:Drosophila Proteins / Q000502:physiology*; D004331:Drosophila melanogaster; D020287:In Situ Nick-End Labeling; D008855:Microscopy, Electron, Scanning; D011679:Pupa / Q000528:radiation effects; D012160:Retina / Q000502:physiology* / Q000528:radiation effects / Q000648:ultrastructure; D015534:Trans-Activators / Q000502:physiology*; D016159:Tumor Suppressor Protein p53; D014466:Ultraviolet Rays
D029721:Drosophila Proteins; D015534:Trans-Activators; D016159:Tumor Suppressor Protein p53; C474203:p53 protein, Drosophila