DNAreparasie

DNAreparasie is the collection of cellular pathways that detect, remove, and correct damage to DNA, preserving genome integrity across cell divisions. DNA can be damaged by replication errors, oxidative stress, ultraviolet light, ionizing radiation, and chemical agents. If unrepaired, damage can cause mutations, genome instability, or cell death, with consequences for health and development.

The major repair pathways include direct reversal, base excision repair, nucleotide excision repair, mismatch repair, and double-strand break repair by homologous recombination or non-homologous end joining. Direct reversal fixes specific lesions by enzymatic reversal of damage, such as removing methyl groups from bases. Base excision repair handles small base changes through glycosylases, AP endonuclease, polymerase, and ligase steps. Nucleotide excision repair removes bulky, helix-distorting lesions via global genome NER or transcription-coupled NER. Mismatch repair corrects replication errors like mispaired bases and small insertion–deletion loops. Double-strand breaks are repaired by homologous recombination, which uses a sister chromatid as a template for high fidelity, or by non-homologous end joining, which ligates ends directly and is more error-prone. Translesion synthesis provides a damage-tolerance route by bypassing lesions with specialized polymerases that may have reduced fidelity.

Repair processes are coordinated by the DNA damage response, which detects damage, activates cell-cycle checkpoints, and recruits repair machinery. Defects in DNA repair compromise genome stability and are linked to cancer predisposition and various developmental and degenerative diseases. Clinically, examples include xeroderma pigmentosum (NER defects), Lynch syndrome (MMR defects), and BRCA1/2 or RAD51 defects affecting homologous recombination. Therapeutically, exploiting repair defects with agents like PARP inhibitors illustrates synthetic lethality in some cancers.