Double-strand breaks (DSBs) are severe forms of DNA damage in which both strands of the DNA double helix are broken. They can result from external factors like ionizing radiation (from medical imaging, environmental sources, or cosmic rays), exposure to chemical mutagens (such as chemotherapeutic drugs and environmental pollutants), and lifestyle factors like smoking. DSBs can also result from internal sources such as replication stress, reactive oxygen species generated during cellular metabolism, and mechanical stress during cell division. In the immune system, DSBs are intentionally created during processes like V(D)J recombination for antibody diversity.