Following siRNA screening, we focussed on validating whether depletion of selected enzymes (OGG1, PARG, Pol β, but also XRCC1) can cause a decrease in cell survival following high-LET protons, whilst having no impact in response to low-LET protons, in both HeLa and HNSCC cells. Here, XRCC1 is linked to head and neck squamous cell carcinoma.