Ionizing Radiation induces cells with past caspase activity that contribute to the adult organ inDrosophilaand show reduced Loss of Heterozygosity

Abstract

AbstractThere is increasing recognition that cells may activate apoptotic caspases but not die, instead displaying various physiologically relevant consequences. We know very little, however, of mechanisms that underlie the life/death decision in a cell that has activated apoptotic caspases. By optimizing a published reporter of past caspase activity, we have been able to visualize such cells that results specifically from exposure to ionizing radiation inDrosophilalarval wing discs. We found that cells withX-ray-inducedpastactivecaspases (XPAC) do not arise at random but are born at specific locations within the developing wing imaginal discs ofDrosophilalarvae. Reduction of apoptotic signaling reduced the prevalence of XPAC cells. Yet, XPAC cells appear in stereotypical patterns that do not follow the pattern of IR-induced apoptosis, suggesting additional controls at play. Functional testing identified the contribution by Wg (Wnt1), Notch and Ras signaling in this process. By following irradiated larvae into adulthood, we found that XPAC cells contribute to the adult wing. To address the relationship between XPAC and genome stability, we combined a reporter for past caspase activity withmwh, an adult marker for Loss of Heterozygosity (LOH). Our data suggest that non-lethal caspase activity safeguards the genome by facilitating DNA repair and reducing LOH after transient exposure to X-rays, identifying a physiological role for non-lethal caspase activity during recovery from radiation damage.Author SummaryCells may activate enzymes needed for apoptosis, a form of cell death, yet not die. We found that cells that lived through the activation of apoptotic enzymes after exposure to ionizing radiation show reduced aberrations in their genomes, suggesting that a near-death experience may benefit the cell.Fit for PLoS GeneticsWe make use ofDrosophilagenetics to address the survival and the fate of cells with past caspase activity, a phenomenon of broad interest. Therefore, this work is a good fit for the readership of PLoS Genetics.