Nucleotide Excision Repair (NER) is a highly conserved and intricate DNA repair mechanism that is essential for maintaining the integrity of the genome in all living organisms. It is a process through which cells recognize, remove, and replace damaged nucleotides in the DNA molecule.
NER is primarily responsible for repairing a wide range of DNA lesions, including pyrimidine (thymine and cytosine) dimers, chemically modified bases, and bulky adducts. These lesions are commonly induced by exposure to environmental agents such as ultraviolet (UV) radiation, certain chemicals, and toxins. If left unrepaired, DNA damage can lead to mutations, chromosomal rearrangements, and ultimately contribute to the development of various diseases, including cancer.
The process of NER involves several coordinated steps. First, damage recognition proteins scan the DNA molecule for abnormalities and identify damaged sites. This is followed by the recruitment of multiple proteins that form a complex around the lesion, creating a DNA repair machinery. This machinery then excises the damaged nucleotides by cleaving the DNA strand on both sides of the lesion. After the lesion removal, the DNA gap is filled by DNA polymerases and sealed by DNA ligases to restore the integrity of the DNA helix.
NER is highly regulated and involves the interaction of numerous proteins, each playing a crucial role in the repair process. Mutations or deficiencies in any of these proteins can lead to DNA repair disorders, such as Xeroderma pigmentosum (XP), Cockayne syndrome (CS), and trichothiodystrophy (TTD), which are characterized by extreme sensitivity to sunlight and an increased risk of skin cancer.
In summary, nucleotide excision repair is a complex and crucial mechanism that maintains genetic stability by removing and replacing damaged
