Repair activity of base and nucleotide excision repair enzymes for guanine lesions induced by nitrosative stress

Toshiaki Nakano, Atsushi Katafuchi, Ryoko Shimizu, Hiroaki Terato, Toshinori Suzuki, Hiroshi Tauchi, Keisuke Makino, Milan Skorvaga, Bennett Van Houten, Hiroshi Ide

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Nitric oxide (NO) induces deamination of guanine, yielding xanthine and oxanine (Oxa). Furthermore, Oxa reacts with polyamines and DNA binding proteins to form cross-link adducts. Thus, it is of interest how these lesions are processed by DNA repair enzymes in view of the genotoxic mechanism of NO. In the present study, we have examined the repair capacity for Oxa and Oxa-spermine cross-link adducts (Oxa-Sp) of enzymes involved in base excision repair (BER) and nucleotide excision repair (NER) to delineate the repair mechanism of nitrosative damage to guanine. Oligonucleotide substrates containing Oxa and Oxa-Sp were incubated with purified BER and NER enzymes or cell-free extracts (CFEs), and the damage-excising or DNA-incising activity was compared with that for control (physiological) substrates. The Oxa-excising activities of Escherichia coli and human DNA glycosylases and HeLa CFEs were 0.2-9% relative to control substrates, implying poor processing of Oxa by BER. In contrast, DNA containing Oxa-Sp was incised efficiently by UvrABC nuclease and SOS-induced E.coli CFEs, suggesting a role of NER in ameliorating genotoxic effects associated with nitrosative stress. Analyses of the activity of CFEs from NER-proficient and NER-deficient human cells on Oxa-Sp DNA confirmed further the involvement of NER in the repair of nitrosative DNA damage.

Original languageEnglish
Pages (from-to)2181-2191
Number of pages11
JournalNucleic Acids Research
Volume33
Issue number7
DOIs
Publication statusPublished - Oct 20 2005
Externally publishedYes

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Guanine
DNA Repair
Enzymes
Cell Extracts
DNA
Nitric Oxide
oxanine
DNA Glycosylases
Escherichia coli
DNA Repair Enzymes
Deamination
Xanthine
Spermine
DNA-Binding Proteins
Polyamines
HeLa Cells
Oligonucleotides
DNA Damage

ASJC Scopus subject areas

  • Genetics

Cite this

Repair activity of base and nucleotide excision repair enzymes for guanine lesions induced by nitrosative stress. / Nakano, Toshiaki; Katafuchi, Atsushi; Shimizu, Ryoko; Terato, Hiroaki; Suzuki, Toshinori; Tauchi, Hiroshi; Makino, Keisuke; Skorvaga, Milan; Van Houten, Bennett; Ide, Hiroshi.

In: Nucleic Acids Research, Vol. 33, No. 7, 20.10.2005, p. 2181-2191.

Research output: Contribution to journalArticle

Nakano, T, Katafuchi, A, Shimizu, R, Terato, H, Suzuki, T, Tauchi, H, Makino, K, Skorvaga, M, Van Houten, B & Ide, H 2005, 'Repair activity of base and nucleotide excision repair enzymes for guanine lesions induced by nitrosative stress', Nucleic Acids Research, vol. 33, no. 7, pp. 2181-2191. https://doi.org/10.1093/nar/gki513
Nakano, Toshiaki ; Katafuchi, Atsushi ; Shimizu, Ryoko ; Terato, Hiroaki ; Suzuki, Toshinori ; Tauchi, Hiroshi ; Makino, Keisuke ; Skorvaga, Milan ; Van Houten, Bennett ; Ide, Hiroshi. / Repair activity of base and nucleotide excision repair enzymes for guanine lesions induced by nitrosative stress. In: Nucleic Acids Research. 2005 ; Vol. 33, No. 7. pp. 2181-2191.
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