Methods disclosed herein capitalize on the discovery that DNA Structure Specific Recognition Proteins (SSRPs) can be induced to bind covalently to genomic lesions formed by chemotherapeutic agents, particularly cisplatin-type agents, by photo-irradiation with ultraviolet light. Methods and compositions based on this discovery are provided for sensitizing particular eukaryotic cells to killing by chemotherapeutic agents, particularly cisplatin-type drugs. Methods and compositions also are provided for potentiating cytotoxicity of a chemotherapeutic agent, particularly a cisplatin-type agent.