Molecular mechanism of global genome nucleotide excision repair.
Nucleotide excision repair (NER) is a multistep process that recognizes and eliminates a wide spectrum of damage causing significant distortions in the DNA structure, such as UV-induced damage and bulky chemical adducts. The consequences of defective NER are apparent in the clinical symptoms of individuals affected by three disorders associated with reduced NER capacities: xeroderma pigmentosum (XP), Cockayne syndrome (CS), and trichothiodystrophy (TTD). These disorders have in common increased sensitivity to UV irradiation, greatly elevated cancer incidence (XP), and multi-system immunological and neurological disorders. The eucaryotic NER system eliminates DNA damage by the excision of 24-32 nt single-strand oligonucleotides from a damaged strand, followed by restoration of an intact double helix by DNA repair synthesis and DNA ligation. About 30 core polypeptides are involved in the entire repair process. NER consists of two pathways distinct in initial damage sensor proteins: transcription-coupled repair (TC-NER) and global genome repair (GG-NER). The article reviews current knowledge on the molecular mechanisms underlying damage recognition and its elimination from mammalian DNA.
Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, prosp. Akad. Lavrentyeva, 8, 630090, Novosibirsk, Russia.
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Petruseva
Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, prosp. Akad. Lavrentyeva, 8, 630090, Novosibirsk, Russia ; Altai State University, Ministry of Education and Science of the Russian Federation, prosp. Lenina, 61, 656049, Barnaul, Russia.
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Evdokimov
Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, prosp. Akad. Lavrentyeva, 8, 630090, Novosibirsk, Russia ; Altai State University, Ministry of Education and Science of the Russian Federation, prosp. Lenina, 61, 656049, Barnaul, Russia ; Novosibirsk State University, Ministry of Education and Science of the Russian Federation, Pirogova Str., 2, 630090, Novosibirsk, Russia.
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Lavrik
molecular mechanisms of damage recognition and elimination; nucleotide excision repair; repair factors