DNA double-strand break (DSB)

DNA double-strand breaks (**DSBs**) are severe forms of DNA damage where both strands of the DNA helix are broken. They represent one of the most cytotoxic types of lesions that can occur within cellular genomes. If unrepaired or misrepaired, they can lead to chromosome fragmentation, loss and translocation events—outcomes that underlie carcinogenesis and other genetic diseases. Cells have evolved complex systems to detect these lesions rapidly and initiate appropriate responses such as cell-cycle arrest, apoptosis, or activation of specialized repair pathways including homologous recombination (HR) and non-homologous end joining (NHEJ). Defects in these processes contribute significantly to cancer predisposition syndromes like Nijmegen breakage syndrome. While not a molecular target per se—since it is a type of damage rather than a discrete molecule—therapeutic strategies often aim either to induce DSBs selectively in tumor cells using chemotherapy/radiation or inhibit their efficient repair by targeting key proteins involved in HR/NHEJ pathways.

Other names

DNA double strand breakDSBDouble-strand break (DSB)DNA DSB

Induction of DSBs by ionizing radiation and radiomimetic drugs for cancer therapy. Example agents: Etoposide, doxorubicin, bleomycin, ionizing radiation. These agents cause cytotoxicity by generating DSBs in rapidly dividing cells. Some targeted therapies inhibit proteins involved in DSB repair pathways to sensitize tumor cells.