Every day, mammalian cells accumulate an estimated 100,000 lesions in their DNA resulting from exposure to reactive oxygen species, chemical deterioration of their bases, and exposure to exogenous agents such as ultraviolet and ionizing radiation. Cells have evolved complex response mechanisms to recognize and repair this injury in order to maintain genomic integrity in the face of this unrelenting assault. The study of DNA damage response has a long and storied history beginning in the 1940s by scientists like Albert Kelner and Renato Dulbecco. Their work revealed the existence of enzymatic photoreactivation and ultimately laid the foundation for the idea that cells respond to DNA damage and that DNA damage repair does exist.