DNAdamage

DNAdamage, often written as DNA damage, refers to modifications that alter the structure or integrity of genetic material. It can affect bases, the sugar-phosphate backbone, or chromosome organization and may disrupt replication or transcription. If unrepaired, damage can introduce mutations or trigger cell cycle arrest or death. The DNA damage response coordinates detection, signaling, and repair to maintain genome stability.

Causes are both endogenous and exogenous. Endogenous sources include replication errors and reactive oxygen species produced by metabolism. Exogenous factors include ultraviolet and ionizing radiation; chemical agents such as alkylating compounds, crosslinking agents, and environmental pollutants.

Common damage types include base modifications (eg, oxidized bases), abasic sites, single-strand breaks, double-strand breaks, and crosslinks. Bulky adducts and UV-induced pyrimidine dimers are typical substrates for specific repair pathways.

Cells detect damage via the DNA damage response, which activates checkpoints and recruits repair systems. Major pathways are base excision repair for small lesions; nucleotide excision repair for bulky damage; mismatch repair for replication errors; and double-strand break repair by homologous recombination or non-homologous end joining. Translesion synthesis can bypass lesions, often with increased mutation risk.

Unrepaired damage can cause mutations, chromosomal rearrangements, or cellular senescence, contributing to aging and cancer. Overall DNA repair capacity influences disease risk and treatment outcomes in conditions associated with genomic instability.

Detection and assessment tools include the comet assay, γ-H2AX foci analysis, sequencing-based mutation profiling, and cytogenetic methods. These approaches are used in research and clinical contexts to study DNA damage and repair efficiency.