<b>Impacts of genetic modifiers on </b><b><i>p53 </i></b><b> driven apoptosis in </b><b><i>Drosophila melanogaster </i></b>

<p dir="ltr">Apoptosis is a tightly regulated form of programmed cell death essential for tissue homeostasis and development. Dysregulation of apoptotic pathways is implicated in numerous diseases including cancers, heart diseases and neurological diseases. In this study, <i>Drosophila melanogaster</i> was used as a model system to investigate genetic modifiers of apoptosis, with a focus on the p53 induced apoptosis. p53 is a tumor suppressor protein that helps maintain body homeostasis and plays a critical role in apoptosis. To understand the influence of genetic background, candidate genes were tested in different eye degeneration models (<i>p53</i>, <i>rpr</i>, <i>Rh1</i>^{<em>G69D</em>}), revealing that some of these genes showed model specific effects and some of them showed opposing effects. Several genes, including<i> art4, fwd and Rox8 were </i>identified as candidate modifiers of the p53 pathway. These genes were initially predicted in a previous computational-based study that correlated expression of these genes to eye size changes. In parallel, the study also validated the role of <i>Cyclin E (CycE)</i>, a well-known cell cycle regulator of apoptosis as a genetic modifier within the p53 pathway. While the knockdown of <i>CycE </i>increased eye size in the <i>p53</i> model, similar effects were not observed in other genetic backgrounds. This suggests that, <i>CycE’s</i> role is both pathway and genetic background specific. Overexpression of <i>CycE</i> uncovered additional functional insights, emphasizing its potential as a useful tool in targeted experimental contexts. Together, these findings reveal the importance of genetic variation in regulating apoptosis and highlight Cyclin E as a key molecular regulator. The use of multiple degenerative models and integration of both computational predictions and experimental validation offer a broader understanding of apoptosis regulation and provide insight into potential therapeutic targets for diseases involving <i>p53</i> dysregulation.</p>