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2005•Nucleic Acids Symposium SeriesOpen access

Activity of nucleotide excision repair enzymes for oxanine cross-link lesions

Toshiaki Nakano, Atsushi Katafuchi, Hiroaki Terato, Toshinori Suzuki, Bennett Van Houten, Hiroshi Ide

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Abstract

Nitric oxide and nitrous acid induce deamination of DNA bases, resulting in uracil, hypoxanthine, xanthine, and oxanine (Oxa) as major damage. Oxa reacts further with polyamines and DNA binding proteins, generating bulky cross-link adducts. Recently we have shown Oxa and cross-link adducts are potentially genotoxic lesions. In the present study, we have assessed the role of base excision repair (BER) and nucleotide excision repair (NER) systems in the repair of Oxa and Oxa-spermine (Oxa-Sp) cross-link adducts. Oxa was very poorly removed from DNA by both BER glycosylases and NER enzymes, whereas Oxa-Sp was efficiently excised by E. coli and human NER enzymes.

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Nitric oxide and nitrous acid induce deamination of DNA bases, resulting in uracil, hypoxanthine, xanthine, and oxanine (Oxa) as major damage. Oxa reacts further with polyamines and DNA binding proteins, generating bulky cross-link adducts. Recently we have shown Oxa and cross-link adducts are potentially genotoxic lesions. In the present study, we have assessed the role of base excision repair (BER) and nucleotide excision repair (NER) systems in the repair of Oxa and Oxa-spermine (Oxa-Sp) cross-link adducts. Oxa was very poorly removed from DNA by both BER glycosylases and NER enzymes, whereas Oxa-Sp was efficiently excised by E. coli and human NER enzymes.

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Available abstract

Nitric oxide and nitrous acid induce deamination of DNA bases, resulting in uracil, hypoxanthine, xanthine, and oxanine (Oxa) as major damage. Oxa reacts further with polyamines and DNA binding proteins, generating bulky cross-link adducts. Recently we have shown Oxa and cross-link adducts are potentially genotoxic lesions. In the present study, we have assessed the role of base excision repair (BER) and nucleotide excision repair (NER) systems in the repair of Oxa and Oxa-spermine (Oxa-Sp) cross-link adducts. Oxa was very poorly removed from DNA by both BER glycosylases and NER enzymes, whereas Oxa-Sp was efficiently excised by E. coli and human NER enzymes.

Key concepts: DNA glycosylase, Nucleotide excision repair, Base excision repair, Deamination, DNA repair, Hypoxanthine, Biochemistry, DNA

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