The nucleotide excision repair NER pathway is a critical DNA repair mechanism that recognizes and repairs various types of DNA damage, including:1. UV-induced damage: This includes cyclobutane pyrimidine dimers CPDs and 6-4 photoproducts 6-4 PPs that result from the covalent bonding of adjacent pyrimidines thymine or cytosine upon exposure to ultraviolet UV radiation.2. Bulky adducts: These are large chemical groups that become covalently attached to DNA bases, often as a result of exposure to environmental mutagens or chemotherapeutic agents. Examples include benzo[a]pyrene diol epoxide BPDE adducts and cisplatin-induced intrastrand crosslinks.3. DNA crosslinks: These are covalent bonds that form between DNA strands, either within the same strand intrastrand crosslinks or between different strands interstrand crosslinks . They can be caused by exposure to certain chemicals or reactive oxygen species.4. Some types of oxidative damage: NER can recognize and repair certain oxidative lesions, such as 8-oxoguanine and thymine glycol.The NER pathway works on a molecular level through the following steps:1. Damage recognition: The first step in NER is the recognition of DNA damage by specific proteins. In global genome NER GG-NER , the XPC-HR23B complex recognizes and binds to the damaged site. In transcription-coupled NER TC-NER , the damage is recognized when RNA polymerase II stalls at the lesion during transcription.2. Recruitment of NER factors: After damage recognition, several NER factors are recruited to the damaged site. These include the TFIIH complex, which contains the helicases XPB and XPD, and the XPA protein.3. DNA unwinding: The XPB and XPD helicases within the TFIIH complex unwind the DNA around the damaged site, creating an open DNA bubble structure. This allows other NER factors to access the damaged strand.4. Damage verification: The XPA protein and the single-stranded DNA-binding protein RPA help verify the presence of damage and stabilize the open DNA structure.5. DNA incision: Two endonucleases, XPF-ERCC1 and XPG, make incisions on either side of the damaged site. XPF-ERCC1 cleaves the DNA strand on the 5' side of the damage, while XPG cleaves the 3' side.6. DNA repair synthesis: After the damaged segment is removed, DNA polymerase or , along with the accessory proteins PCNA and RFC, fill in the gap by synthesizing new DNA using the undamaged strand as a template.7. DNA ligation: Finally, DNA ligase I or III, in complex with the XRCC1 protein, seals the remaining nick in the DNA backbone, completing the repair process.Overall, the NER pathway plays a crucial role in maintaining genomic integrity by recognizing and repairing various types of DNA damage that can lead to mutations and genomic instability if left unrepaired.