Radiation induces DNA breaks, the most dangerous type of DNA damage. Efficient repair of these breaks leads to cancer cell survival and treatment resistance. While progress has been made in establishing a connection between these processes, critical mechanistic links require elucidation. This knowledge is necessary in order to develop targeted therapy to prevent treatment resistance in cancer. The goal of the proposed study is to address the mechanism of DNA repair and cell survival in head and neck cancer. This research is significant because it is expected to reveal mechanisms that can be targeted to promote radiation-induced cell death. The long term goal is to develop mechanism-based strategies for sensitizing tumors to radiation.