DNA repair is the set of molecular processes that detect and correct damage in DNA, preserving genome stability and preventing disease. DNA is constantly harmed by external agents such as ultraviolet light, ionizing radiation and chemicals, as well as internal sources like reactive oxygen species and replication errors. Unrepaired damage can lead to mutations, cell death or cancer.

Cells use several major pathways tailored to specific types of lesions. Base excision repair fixes small, non helix distorting base damage, such as oxidation or deamination, using DNA glycosylases, endonucleases, polymerases and ligases. Nucleotide excision repair removes bulky lesions like UV induced thymine dimers by cutting out a short single stranded DNA segment surrounding the damage and then resynthesizing it.

Mismatch repair corrects replication errors, such as mispaired bases and small insertions or deletions that escape the proofreading activity of DNA polymerases. Double strand breaks, which are particularly dangerous, are repaired mainly by non homologous end joining and homologous recombination. Non homologous end joining rapidly ligates broken ends, often with small sequence changes. Homologous recombination uses an intact sister chromatid as a template for error free repair.

Cells also mount a broader DNA damage response. Damage sensors trigger signaling cascades that halt the cell cycle, giving time for repair or leading to apoptosis if the damage is irreparable. Defects in repair genes underlie many inherited cancer predisposition syndromes and contribute to aging.

Understanding DNA repair has led to therapies that exploit repair weaknesses in tumors, such as PARP inhibitors in cancers with BRCA mutations, and is guiding development of radiotherapy and chemotherapy strategies.