DNA repair | Nucleotide Excision Repair in Eukaryotes

Nucleotide excision repair (NER) is a versatile DNA repair system that removes a wide variety of DNA-distorting lesions, such as UV-induced photoproducts, cross-links induced by the antitumor agent cisplatin, and bulky base adducts induced by numerous chemical compounds. One of the most intriguing aspects of NER is that it is capable of discriminating all these different types of damage from a large excess of undamaged DNA, which moreover in the case of eukaryotic cells is densely packed into chromatin. For scanning the DNA for presence of damage, two subpathways are used. In the transcription-coupled repair pathway, the RNA polymerase acts as the initial sensor for lesions that are present in the transcribed strand. Transcription is arrested at a damaged site and subsequently repair proteins recognize the stalled RNA polymerase. For repair of the nontranscribed parts of the DNA (global genome repair), specific damage-recognition factors search the genome for aberrations. For both repair pathways, the initial damage recognition is followed by a common cascade of events where presence of the damage is verified and part of the damaged strand containing the lesion is removed.