Nucleotide Excision Repair

Nucleotide excision repair, or NER, fixes bulky DNA lesions caused by UV radiation and chemical carcinogens.

These bulky lesions, such as pyrimidine dimers, distort the DNA helix and interfere with DNA replication and transcription.

In the bacterium E. coli, the repair proteins UvrA and UvrB form a complex that scans genomic DNA for structural lesions.

Once the complex encounters a lesion, UvrA dissociates, causing UvrB to bind tightly to the distorted DNA.

The DNA-bound UvrB then recruits UvrC, an endonuclease, which makes incisions on either side of the lesion.

Next, the UvrD helicase unwinds the DNA and releases the fragment carrying the lesion.

Following excision, DNA polymerase fills the gap with new complementary nucleotides. DNA ligase then seals the gap between the new and old DNA, completing the repair.

Alternatively, if an actively transcribing RNA polymerase stalls at a bulky lesion, the stalled complex promotes recruitment of the UvrA–UvrB repair machinery to the site.

This initiates transcription-coupled nucleotide excision repair, which proceeds in the same manner as regular NER and allows transcription to continue.