Excessive protein stability plays a deleterious role in multiple physiological conditions, such as
neurodegeneration. Protein quality control (PQC) regulates protein stability, promoting timely
decay and preventing protein aggregation. Studies of the last years demonstrated that PQC is
intimately connected to the DNA damage response (DDR) and that insufficient activity of one
process negatively impacts the other. Despite these intriguing observations, the direct impact of
DDR on global protein stability is not well established. This project aims to close this gap by
elucidating global alterations in protein stability upon exposure to different types of genotoxic
stress. Our preliminary data suggest that these conditions negatively impact proteasome activity,
resulting in the significantly increased stability of reporter proteins. To facilitate this study, we
aim to develop a novel method that will enable dynamic chasing of protein stability in single
living cells and discover the precise timing of the observed phenomenon. Subsequent
proteome-wide validations will determine the scope of this phenomenon and empower us to
progress toward a collaborative effort aiming to determine its role in neurodegeneration. This
project aims to establish a novel link between DNA damage and protein stability and uncover its
role in pathological conditions.