Despite the proliferation of novel therapies such as immunotherapy or targeted therapies, radiation and chemotherapy remain the frontline treatment for cancer patients. About half of all patients still receive radiation and 60-80 percent receive chemotherapy. Both radiation and chemotherapy work by damaging DNA, taking advantage of a vulnerability specific to cancer cells. Healthy cells are more likely to survive radiation and chemotherapy since their mechanisms for identifying and repairing DNA damage are intact. In cancer cells, these repair mechanisms are compromised by mutations. When cancer cells cannot adequately respond to the DNA damage caused by radiation and chemotherapy, ideally, they undergo apoptosis or die by other means. However, there is another fate for cells after DNA damage: senescence — a state where cells survive, but stop dividing. Senescent cells’ DNA has not been damaged enough to induce apoptosis but is too damaged to support cell division. While senescent ca
Living organisms are continuously exposed to a myriad of DNA-damaging agents that can impact health and modulate disease states. However, robust DNA repair and damage-bypass mechanisms faithfully protect the DNA by either removing or tolerating the damage to ensure overall survival. Deviations in this fine-tuning are known to destabilize cellular metabolic homeostasis, as exemplified in diverse cancers where disruption or deregulation of DNA repair pathways results in genome instability. Because routinely used biological, physical and chemical agents impact human health, testing their genotoxicity and regulating their use have become important. In this introductory review, we will delineate mechanisms of DNA damage and the counteracting repair/tolerance pathways to provide insights into the molecular basis of genotoxicity in cells that lay the foundation for subsequent articles in this issue. Introduction Preserving genomic sequence information in living organisms is important for the