doublestrandbreak

Doublestrandbreak, commonly written as double-strand break (DSB), is a form of DNA damage in which both strands of the DNA double helix are cleaved. DSBs can arise from endogenous processes such as reactive oxygen species produced during metabolism, replication fork collapse, and programmed breaks during meiosis or immune diversification, as well as exogenous agents including ionizing radiation and certain chemicals. If unrepaired, DSBs threaten genome stability and can trigger cell death, senescence, or chromosomal rearrangements and mutations.

Repair and response: Cells employ DNA damage response pathways to detect and repair DSBs. The two main repair pathways are non-homologous end joining (NHEJ), which ligates broken ends directly and can be error-prone, and homologous recombination (HR), which uses a sister chromatid as a template for accurate repair during S and G2 phases. Alternative end-joining and microhomology-mediated end joining operate when canonical pathways are compromised. The choice of pathway is influenced by cell cycle stage and chromatin context.

Detection and implications: DSBs activate signaling through sensor proteins such as the MRN complex and kinases like ATM and ATR, leading to cell cycle checkpoints and repair gene transcription. Experimental detection often uses γ-H2AX foci, 53BP1 localization, or neutral comet assays.

Clinical and research relevance: DSB induction is central to radiotherapy and many chemotherapeutics, and is also the mechanism by which genome editing tools such as CRISPR-Cas9 generate edits. Defects in HR (e.g., BRCA1/2 mutations) or NHEJ components can drive cancer development and influence treatment responses; therapies like PARP inhibitors exploit these defects.