Nucleotide excision repair (NER) removes bulky DNA lesions that distort the local double helix rather than targeting one specific damaged-base chemistry.

A classic example is a UV-induced pyrimidine dimer, in which neighboring bases on one DNA strand become covalently linked. The lesion bends or distorts the duplex and can obstruct DNA or RNA polymerases.

Repair removes an oligonucleotide segment

NER follows a different strategy from base excision repair.

1. Repair proteins detect abnormal local DNA structure.
2. The damaged strand is cut on both sides of the lesion.
3. A short oligonucleotide, meaning a short nucleotide segment, containing the lesion is removed.
4. DNA polymerase fills the resulting gap by copying the intact opposite strand.
5. DNA ligase seals the remaining backbone nick.

Schematically:

intact strand:  -------------------------
damaged strand: -------[lesion]----------
                       ↓
              cut on both sides
                       ↓
                remove short segment
                       ↓
              DNA polymerase + ligase
                       ↓
                 restored duplex

Recognition can be structure-based

The strength of NER is that it does not need a different glycosylase for every possible bulky chemical modification. Many chemically distinct lesions can be repaired if they create a DNA structure that the repair machinery recognizes as abnormal.

NER and BER solve different problems

• Base excision repair usually removes one chemically abnormal base first and then repairs the resulting small gap.
• Nucleotide excision repair removes a short stretch of nucleotides surrounding a helix-distorting lesion.

Both pathways exploit the same informational advantage of double-stranded DNA: an intact complementary strand can guide accurate resynthesis after damaged material is removed.

NER therefore protects genome information by converting a difficult structural lesion into an ordinary template-directed gap-filling problem.