Nucleotide Excision Repair: from DNA Damage Processing to Human Disease

摘要: A network of DNA damage surveillance systems warrants genomic stability under conditions where cells and organisms are continuously exposed to damaging agents. This includes repair pathways, but also signaling pathways that activate cell cycle checkpoints, apoptosis, transcription, chromatin remodeling. Among the various nucleotide excision (NER) is a highly versatile evolutionary conserved pathway with an intriguing wide substrate specificity; this removes structurally unrelated bulky lesions from genome such as sunlight induced photolesions, adducts formed by polycyclic aromatic hydrocarbons, cisplatin intrastrand crosslinks, alkylation products. The common features these variable degree helix distortion inflicted their potency block replication transcription. importance functional NER for human health highlighted existence rare autosomal recessive disorders xeroderma pigmentosum (XP). Affected individuals, characterized defect in NER, suffer hypersensitivity display strongly enhanced cancer susceptibility parts skin. Mammalian involves multiple proteins (in excess 30) carries out reaction orchestrated fashion.