Degradation and modification of nucleic acids

Adams, Roger; Knowler, John T.; Leader, David P.

doi:10.1007/978-94-009-4103-8_4

Cited by 6 publications

(4 citation statements)

References 215 publications

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“…The breadth of DNA adductomics is dependent on the efficiency of digestion of chemically modified DNA, and adducts of different structures may require different cocktails of enzymes for quantitative digestion of DNA to the mononucleoside adducts (typical combinations of enzymes are nucleases or DNases used with phosphodiesterases and alkaline phosphatase). 86 After DNA hydrolysis, DNA adducts must be enriched and purified from the nonmodified deoxynucleosides that are present in 10 6 to 10 9 excess. Therefore, the DNA hydrolysates are often processed by solid-phase extraction cleanup steps to enrich DNA adducts and to remove the bulk of unmodified nucleosides, proteins, inorganic salts, and other sample components that can interfere with MS analysis.…”

Section: Sample Source and Preparationmentioning

confidence: 99%

“…More DNA is required for adductomic analysis than for targeted DNA adduct quantitation using the same instrumentation and analytical parameters. The breadth of DNA adductomics is dependent on the efficiency of digestion of chemically modified DNA, and adducts of different structures may require different cocktails of enzymes for quantitative digestion of DNA to the mononucleoside adducts (typical combinations of enzymes are nucleases or DNases used with phosphodiesterases and alkaline phosphatase) …”

Section: Sample Source and Preparationmentioning

confidence: 99%

See 1 more Smart Citation

DNA Adductomics

Balbo

Turesky²,

Villalta³

2014

Chem. Res. Toxicol.

161

179

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Systems toxicology is a broad based approach to describe many of the toxicological features that occur within a living system under stress or subjected to exogenous or endogenous exposures. The ultimate goal is to capture an overview of all exposures and the ensuing biological responses of the body. The term “exposome” has been employed to refer to the totality of all exposures and systems toxicology investigates how the exposome influences health effects and consequences of exposures over a lifetime. The tools to advance systems toxicology include high-throughput transcriptomics, proteomics, metabolomics and adductomics, which is still in its infancy. A well-established methodology for the comprehensive measurement of DNA damage resulting from every day exposures is not fully developed. During the past several decades, the 32P-postlabeling technique has been employed to screen the damage to DNA induced by multiple classes of genotoxicants; however, more robust, specific, and quantitative methods have been sought to identify and quantify DNA adducts. While triple quadrupole and ion trap mass spectrometry, in particular when using multistage scanning (LC-MSn), have shown promise in the field of DNA adductomics, it is anticipated that high resolution and accurate mass LC-MSn instrumentation will play a major role in assessing global DNA damage. Targeted adductomics should benefit greatly from improved triple quadrupole technology. Once the analytical MS methods are fully mature, DNA adductomics along with other –omics tools will contribute greatly to the field of systems toxicology.

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Section: Sample Source and Preparationmentioning

confidence: 99%

Section: Sample Source and Preparationmentioning

confidence: 99%

DNA Adductomics

Balbo

Turesky²,

Villalta³

2014

Chem. Res. Toxicol.

161

179

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“…Under reaction conditions similar to those found inside human cells, the spontaneous cleavage of RNA typically occurs with a rate constant of ∼10 −7 min −1 (Li and Breaker 1999), which reflects a half-life of >1 year. In comparison, pancreatic ribonuclease A (RNase A) accelerates this phosphoester transfer reaction by >12 orders of magnitude (Adams et al 1992;Raines 1998), resulting in a half-life for an RNA linkage that is measured in microseconds. RNase A is thought to achieve this impressive rate acceleration by using four catalytic strategies ( Fig.…”

Section: Introductionmentioning

confidence: 99%

Ribozyme speed limits

Emilsson¹,

Nakamura²,

Roth³

et al. 2003

RNA

201

273

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The speed at which RNA molecules decompose is a critical determinant of many biological processes, including those directly involved in the storage and expression of genetic information. One mechanism for RNA cleavage involves internal phosphoester transfer, wherein the 2-oxygen atom carries out an S N 2-like nucleophilic attack on the adjacent phosphorus center (transesterification). In this article, we discuss fundamental principles of RNA transesterification and define a conceptual framework that can be used to assess the catalytic power of enzymes that cleave RNA. We deduce that certain ribozymes and deoxyribozymes, like their protein enzyme counterparts, can bring about enormous rate enhancements.

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“…The extracted and purified DNA then needs to be digested to release the DNA adducts. For digestion, a cocktail which is comprised of a combination of nucleases (cleave the phosphodiester bond of nucleic acids including DNA and RNA), DNases (cleave the phosphodiester bond of DNA only), phosphodiesterase (break any phosphodiester bond) and alkaline phosphatase (removes phosphate group from nucleic acids) is normally used [33]. During digestion, the DNA is normally broken down into mononucleotides dA, dG, dC, dT along with the adducted mononucleotides such as dG-C8-4-ABP.…”

Section: Steps Of Analyzing Dna Adductsmentioning

confidence: 99%

Recent technical and biological development in the analysis of biomarker N -deoxyguanosine-C8-4-aminobiphenyl

Chen

Zhang

Vouros

2018

Journal of Chromatography B

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4-Aminobiphenyl (4-ABP) which is primarily formed during tobacco combustion and overheated meat is a major carcinogen responsible for various cancers. Its adducted form, N-deoxyguanosine-C8-4-aminobiphenyl (dG-C8-4-ABP), has long been employed as a biomarker for assessment of the risk for cancer. In this review, the metabolism and carcinogenisity of 4-ABP will be discussed, followed by a discussion of the current common approaches of analyzing dG-C8-4-ABP. The major part of this review will be on the history and recent development of key methods for detection and quantitation of dG-C8-4-ABP in complex biological samples and their biological applications, from the traditional P-postlabelling and immunoassay methods to modern liquid chromatography-mass spectrometry (LC-MS) with the latter as the focus. Many vital biological discoveries based on dG-C8-4-ABP have been published by using the nanoLC-MS with column switching platform in our laboratory, which has also been adopted and further improved by many other researchers. We hope this review can provide a perspective of the challenges that had to be addressed in reaching our present goals and possibly bring new ideas for those who are still working on the frontline of DNA adducts area.

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Degradation and modification of nucleic acids

Cited by 6 publications

References 215 publications

DNA Adductomics

DNA Adductomics

Ribozyme speed limits

Recent technical and biological development in the analysis of biomarker N -deoxyguanosine-C8-4-aminobiphenyl

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