Quantitative determination of oxidative base damage in DNA by stable isotope‐dilution mass spectrometry

Dizdaroglu, M.

doi:10.1016/0014-5793(93)81120-o

Cited by 154 publications

(87 citation statements)

References 26 publications

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“…Isodialuric acid was 5 then represents the combined excision of both cytoalso stable in contrast to the reported oxidation of dia-sine and uracil 5,6-glycols by the enzyme. In contrast, luric acid to alloxan (38). Thus, we conclude that the it is unlikely that either 5-hydroxycytosine (4) or 5-presence of 1-5 and 8 in the supernatant fraction of hydroxyuracil (2) arises from this pathway.…”

Section: Analyses Of Eight Cytosine Base Modifications By Gc/ Fig 2mentioning

confidence: 64%

Excision of Oxidative Cytosine Modifications from γ-Irradiated DNA byEscherichia coliEndonuclease III and Human Whole-Cell Extracts

Wagner

Blount

Weinfeld³

1996

Analytical Biochemistry

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Section: Analyses Of Eight Cytosine Base Modifications By Gc/ Fig 2mentioning

confidence: 64%

Excision of Oxidative Cytosine Modifications from γ-Irradiated DNA byEscherichia coliEndonuclease III and Human Whole-Cell Extracts

Wagner

Blount

Weinfeld³

1996

Analytical Biochemistry

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“…Supernatant fractions were lyophilized, trimethylsilylated, and analyzed by GC/MS as described (32). For identification and quantification, selected-ion monitoring was used to monitor the characteristic ions of trimethylsilylated 8-OHGua, FapyAde, and FapyGua and their stable isotope-labeled analogues as internal standards (36).…”

Section: Methodsmentioning

confidence: 99%

Cockayne Syndrome Group B Protein Stimulates Repair of Formamidopyrimidines by NEIL1 DNA Glycosylase

Müftüoğlu

Souza-Pinto

Doğan

et al. 2009

Journal of Biological Chemistry

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Cockayne syndrome (CS) 6 is a segmental premature aging syndrome with progressive neurological degeneration (1). CS is caused by mutations in CS complementation groups A (CSA) or B (CSB) genes (2, 3). Approximately 80% of CS patients have mutations in the CSB gene, which encodes a 168-kDa protein belonging to the SWI/SNF2 family of chromatin remodeling proteins (4). Cells from CS patients are hypersensitive to UV radiation-induced DNA damage, and the CSB protein is required for the transcription-coupled nucleotide excision repair of UV radiation-induced DNA lesions (cyclobutane pyrimidine dimers and 6-pyrimidine-4-pyrimidone products) (5). CSB is also believed to play a role in transcription elongation and interacts with the RNA polymerase II elongation complex (6). The molecular basis of the progressive neurological defects in CS patients, however, remains unknown; it has been proposed that neurological symptoms in CS may be due to defective repair and/or processing of oxidative DNA damage in CSB-deficient cells (7).Oxidative DNA damage can be caused by endogenous and exogenous agents. Reactive oxygen species, including highly reactive hydroxyl radicals, are formed as byproducts of normal metabolism, mostly during the process of mitochondrial respiration. It has been estimated that up to 2% of all the O 2 consumed by respiration may be released as reactive oxygen species (8, 9). The central nervous system relies exclusively on mitochondria to generate ATP through oxidative metabolism. As a result, neurons are susceptible to increased levels of oxidative stress, and elevated levels of reactive oxygen species have been implicated in the etiology of neurodegenerative diseases including Alzheimer, Parkinson, and Huntington diseases and amyotrophic lateral sclerosis (for a review, see Ref. 10).Hydroxyl radicals attack DNA bases and the sugar-phosphate DNA backbone, generating modified bases and singlestranded DNA (ssDNA) breaks, respectively (11). Many oxida-

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“…Supernatant fractions were lyophilized, trimethylsilylated, and analyzed by GC/MS as described (24). For identification and quantification, selected-ion monitoring was used to monitor the characteristic ions of trimethylsilylated FapyA and FapyG and their stable isotopelabeled analogues (25).…”

Section: Analysis By Liquid Chromatography/mass Spectrometry (Lc/ms) mentioning

confidence: 99%

Repair of Formamidopyrimidines in DNA Involves Different Glycosylases

Souza-Pinto

Haraguchi

et al. 2005

Journal of Biological Chemistry

181

148

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The oxidatively induced DNA lesions 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyG) and 4,6-diamino-5-formamidopyrimidine (FapyA) are formed abundantly in DNA of cultured cells or tissues exposed to ionizing radiation or to other free radical-generating systems. In vitro studies indicate that these lesions are miscoding, can block the progression of DNA polymerases, and are substrates for base excision repair. However, no study has yet addressed how these lesions are metabolized in cellular extracts. The synthesis of oligonucleotides containing FapyG and FapyA at defined positions was recently reported. These constructs allowed us to investigate the repair of Fapy lesions in nuclear and mitochondrial extracts from wild type and knock-out mice lacking the two major DNA glycosylases for repair of oxidative DNA damage, OGG1 and NTH1. The background level of FapyG/FapyA in DNA from these mice was also determined. Endogenous FapyG levels in liver DNA from wild type mice were significantly higher than 8-hydroxyguanine levels. FapyG and FapyA were efficiently repaired in nuclear and mitochondrial extracts from wild type animals but not in the glycosylasedeficient mice. Our results indicated that OGG1 and NTH1 are the major DNA glycosylases for the removal of FapyG and FapyA, respectively. Tissue-specific analysis suggested that other DNA glycosylases may contribute to FapyA repair when NTH1 is poorly expressed. We identified NEIL1 in liver mitochondria, which could account for the residual incision activity in the absence of OGG1 and NTH1. FapyG and FapyA levels were significantly elevated in DNA from the knock-out mice, underscoring the biological role of OGG1 and NTH1 in the repair of these lesions.A large number of DNA base modifications are formed by oxidative damage to DNA (for review, see Ref. 1). Some of these lesions are generated at high rates, even in the absence of exogenous DNA-damaging agents. For instance, it was estimated that 100 -500 8-hydroxyguanines 3 are formed per day in a human cell (2). 8-oxoG is one of the most studied DNA lesions, and it is often used as a biomarker of oxidative DNA damage. However, ring-opened formamidopyrimidine lesions, 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyG) and 4,6-diamino-5-formamidopyrimidine (FapyA), are formed at equal or higher levels than 8-oxoG after oxidative stress (3-5). These lesions result from hydroxyl radical attack on guanine and adenine, respectively, followed by one-electron reduction of the hydroxyl adduct radicals (1), which are also intermediates in the formation of 8-oxoG and 8-oxoA (6). Formation of Fapy lesions in DNA upon UV radiation has also been reported (7). FapyA (8) and FapyG (9) are miscoding in vitro, both directing the preferential misincorporation of adenine opposite the lesions by a bacterial DNA polymerase (Klenow exo Ϫ ). Experiments using the methylated analogue of FapyG, i.e. 2,6-diamino-4-hydroxy-5-Nmethylformamidopyrimidine (Me-FapyG), have suggested that formamidopyrimidines might also constitute blocks to DNA poly...

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Quantitative determination of oxidative base damage in DNA by stable isotope‐dilution mass spectrometry

Cited by 154 publications

References 26 publications

Excision of Oxidative Cytosine Modifications from γ-Irradiated DNA byEscherichia coliEndonuclease III and Human Whole-Cell Extracts

Excision of Oxidative Cytosine Modifications from γ-Irradiated DNA byEscherichia coliEndonuclease III and Human Whole-Cell Extracts

Cockayne Syndrome Group B Protein Stimulates Repair of Formamidopyrimidines by NEIL1 DNA Glycosylase

Repair of Formamidopyrimidines in DNA Involves Different Glycosylases

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