Processing and Consequences of Oxidative DNA Base Lesions

Wallace, Susan S.; Harrison, Louis; Jiang, Dongyan; Blaisdell, Jeffrey O.; Purmal, Andrei A.; Hatahet, Zafer

doi:10.1007/978-1-4615-4865-2_34

Cited by 4 publications

(3 citation statements)

References 58 publications

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“…Under oxidative stress conditions such as ionizing radiation and exposure to H 2 O 2 , S. typhimurium glycosylase mutants were also comparable to E. coli glycosylase mutants (Fig. 4; Cunningham and Weiss, 1985; Jiang et al ., 1997; Wallace et al ., 1999).…”

Section: Discussionsupporting

confidence: 91%

The role of DNA base excision repair in the pathogenesis of Salmonella enterica serovar Typhimurium

Suvarnapunya

Lagassé

Stein³

2003

Molecular Microbiology

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SummaryThe intracellular pathogen, Salmonella enterica serovar Typhimurium, is able to proliferate in phagocytes, although reactive oxygen and nitrogen intermediates are lethal to most phagocytosed bacteria. To determine whether repair of oxidatively damaged DNA is involved in S. typhimurium intramacrophage proliferation, null mutants of the DNA base excision repair (BER) system were generated. These mutants were deficient in dis- D xth/nfo was 12-fold attenuated compared with wild type. These data indicate that DNA oxidation is a mechanism that macrophages use to damage intracellular Salmonella , and suggest that BER-mediated repair of this damage may be important in the establishment of Salmonella infection. We speculate that adaptation to a pathogenic lifestyle may influence the acquisition and retention of redundant BER enzymes.

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Section: Discussionsupporting

confidence: 91%

The role of DNA base excision repair in the pathogenesis of Salmonella enterica serovar Typhimurium

Suvarnapunya

Lagassé

Stein³

2003

Molecular Microbiology

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“…We and others have previously shown that E. coli mutants lacking both endo III and endo VIII (nth nei) are hypersensitive to the lethal effects of ionizing radiation (25) and hydrogen peroxide (51,60), indicating that these enzymes are responsible for removing potentially lethal oxidative lesions in DNA. This is in contrast to mutants lacking Fpg protein, which are not hypersensitive to the lethal effects of ionizing radiation or hydrogen peroxide (5,60). nth nei double mutants also exhibit increased spontaneous mutation frequency, as determined by both forward mutation and reversion assays (24).…”

Section: Resultsmentioning

confidence: 99%

A Novel Role for Escherichia coli Endonuclease VIII in Prevention of Spontaneous G→T Transversions

1999

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In the bacterium Escherichia coli, oxidized pyrimidines are removed by two DNA glycosylases, endonuclease III and endonuclease VIII (endo VIII), encoded by the nth and neigenes, respectively. Double mutants lacking both of these activities exhibit a high spontaneous mutation frequency, and here we show that all of the mutations observed in the double mutants were G:C→A:T transitions; no thymine mutations were found. These findings are in agreement with the preponderance of C→T transitions in the oxidative and spontaneous mutational databases. The major oxidized purine lesion in DNA, 7,8-dihydro-8-oxoguanine (8-oxoG), is processed by two DNA glycosylases, formamidopyrimidine DNA glycosylase (Fpg), which removes 8-oxoG opposite C, and MutY DNA glycosylase, which removes misincorporated A opposite 8-oxoG. The high spontaneous mutation frequency previously observed in fpg mutY double mutants was significantly enhanced by the addition of the neimutation, suggesting an overlap in the substrate specificities between endo VIII and Fpg/MutY. When the mutational specificity was examined, all of the mutations observed were G:C→T:A transversions, indicating that in the absence of Fpg and MutY, endo VIII serves as a backup activity to remove 8-oxoG. This was confirmed by showing that, indeed, endo VIII can recognize 8-oxoG in vitro.

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“…Although Nth is widely distributed over all three kingdoms, Nei is only sparsely represented and found in some ␥-proteobacteria, actinomycetes, and vertebrates (6). Escherichia coli lacking both Nth and Nei exhibit a high spontaneous mutation frequency and are hypersensitive to hydrogen peroxide and ionizing radiation (8)(9)(10)(11).…”

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confidence: 99%

The crystal structure of human endonuclease VIII-like 1 (NEIL1) reveals a zincless finger motif required for glycosylase activity

Doublié

Bandaru

Bond

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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135

194

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In prokaryotes, two DNA glycosylases recognize and excise oxidized pyrimidines: endonuclease III (Nth) and endonuclease VIII (Nei). The oxidized purine 8-oxoguanine, on the other hand, is recognized by Fpg (also known as MutM), a glycosylase that belongs to the same family as Nei. The recent availability of the human genome sequence allowed the identification of three human homologs of Escherichia coli Nei. We report here the crystal structure of a human Nei-like (NEIL) enzyme, NEIL1. The structure of NEIL1 exhibits the same overall fold as E. coli Nei, albeit with an unexpected twist. Sequence alignments had predicted that NEIL1 would lack a zinc finger, and it was therefore expected to use a different DNA-binding motif instead. Our structure revealed that, to the contrary, NEIL1 contains a structural motif composed of two antiparallel ␤-strands that mimics the antiparallel ␤-hairpin zinc finger found in other Fpg͞Nei family members but lacks the loops that harbor the zinc-binding residues and, therefore, does not coordinate zinc. This ''zincless finger'' appears to be required for NEIL1 activity, because mutating a very highly conserved arginine within this motif greatly reduces the glycosylase activity of the enzyme.

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Processing and Consequences of Oxidative DNA Base Lesions

Cited by 4 publications

References 58 publications

The role of DNA base excision repair in the pathogenesis of Salmonella enterica serovar Typhimurium

The role of DNA base excision repair in the pathogenesis of Salmonella enterica serovar Typhimurium

A Novel Role for Escherichia coli Endonuclease VIII in Prevention of Spontaneous G→T Transversions

The crystal structure of human endonuclease VIII-like 1 (NEIL1) reveals a zincless finger motif required for glycosylase activity

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