225B Poster - 01. Cell Stress and cell death
Friday April 08, 2:00 PM - 4:00 PM
Mechanisms for culling of Drosophila wing disc cells with loss-of-heterozygosity after irradiation
Authors: Jeremy Brown 1; Inle Bush 1; Justine Bozon 1; Tin Tin Su 1,2
Affiliations: 1) Department of Molecular, Cellular and Developmental Biology, University of Colorado Boulder, Boulder, CO; 2) University of Colorado Cancer Center, Anschutz Medical Campus, Denver, CO
Keywords: h. other (DNA damage response); c. RNAi
The ability of ionizing radiation (IR) to induce cell death is the basis for radiotherapy which is used to treat approximately half of cancer patients. IR causes DNA damage and events such as loss of heterozygosity (LOH). Undesirable effects such as oncogenesis can be promoted by functional loss of a tumor suppressor due to IR induced LOH. To study LOH events we use a cell-autonomous fluorescence-based system that uses the QF/QS transcriptional module. This allows our studies to expand into larval, pupal, and adult stages of Drosophila wing development. In parallel with QF/QS, we use the GAL4/UAS system to knockdown or overexpress genes of interest and we use engrailed-GAL4 to restrict UAS expression to the posterior compartment of the wing disc. In our studies, we compare the number and area of LOH clones found in the posterior to those of the anterior compartment after IR. Previously with these tools, we identified two distinct phases of LOH cell culling during development with p53-dependent as well as p53-independent mechanisms (Brown et al., PLoS Genetics, 2020, PMID: 33075096). Today, we will present recent data on LOH culling regarding genes involved with various cellular processes including Apoptosis-induced-Proliferation, ROS signaling, JNK and p53 signaling, and DNA repair.