nucleotideexcision

Nucleotide excision repair, often abbreviated as NER, is a cellular mechanism that corrects a variety of DNA damage. This damage can include bulky lesions that distort the DNA helix, such as those caused by UV radiation or certain chemical mutagens. The NER pathway is crucial for maintaining genomic integrity and preventing mutations that could lead to diseases like cancer.

The NER process begins with the recognition of the damaged DNA segment by specific repair proteins. These proteins scan the DNA and identify distortions in the double helix. Once the damage is located, a complex of proteins assembles at the site. This complex then makes incisions on both sides of the damaged nucleotide. Following the incisions, a short oligonucleotide containing the damaged DNA is removed. The gap is then filled in by a DNA polymerase, using the undamaged strand as a template. Finally, a DNA ligase seals the nick in the DNA backbone, completing the repair.

There are two main sub-pathways of NER: transcription-coupled repair (TCR) and global genome repair (GGR). TCR specifically targets DNA damage that is obstructing transcription, ensuring that essential genes can still be transcribed. GGR repairs damage throughout the entire genome, regardless of transcriptional activity. Both pathways involve a conserved set of core proteins but differ in their initial damage recognition steps. Defects in NER genes are associated with a range of genetic disorders, most notably xeroderma pigmentosum, a condition characterized by extreme sensitivity to sunlight and a significantly increased risk of skin cancer.