DNA is a reactive molecule and it is estimated that more than 20 thousand lesions are induced endogenously per cell per day, besides other induced by exogenous agents such as ultraviolet light exposure, resulting in physical blockage of DNA replication and transcription machineries. In response to DNA damage, cells activate responses that promote cell cycle regulation and DNA repair, avoiding replication or mitosis catastrophe. If DNA damage exceeds DNA repair capacity, cells induce cell death as last resort. The importance of responses to DNA damage is exemplified by human syndromes with premature aging phenotype and increased risk of cancer, and their study could contribute to understanding of tumorigenesis and development of improved therapies.