Nucleotide Excision Repair

Nucleotide excision repair (NER) is a DNA repair pathway that removes bulky lesions — pyrimidine dimers caused by UV light, chemical adducts, and cross-links — that distort the DNA helix and block replication or transcription. Unlike mismatch repair, which corrects base-pairing errors, NER recognizes damage that alters the physical structure of the double helix.

The mechanism involves damage recognition, dual incisions around the lesion (typically 24-32 nucleotides apart in eukaryotes), excision of the damaged oligonucleotide, gap-filling synthesis, and ligation. In humans, the NER machinery includes over 30 proteins, and defects cause xeroderma pigmentosum — a syndrome of extreme UV sensitivity and cancer predisposition.

NER and mismatch repair are not parallel systems. They are sequential layers: NER handles environmental damage, mismatch repair handles replication errors. The cell's information-preservation strategy is not a single mechanism but a hierarchy of surveillance systems, each tuned to a different threat. The hierarchy itself is the design.