scholarly journals Oxidation of DNA bases, deoxyribonucleosides and homopolymers by peroxyl radicals

1998 ◽  
Vol 335 (2) ◽  
pp. 233-240 ◽  
Author(s):  
Tiberiu SIMANDAN ◽  
Jing SUN ◽  
Thomas A. DIX
Keyword(s):  
Oxidative Damage ◽  
Cellular Systems ◽  
Peroxyl Radicals ◽  
Dna Bases ◽  
Molecular Probe ◽  
Mutagenic Potential ◽  
Dna Base ◽  
Disease Initiation ◽  
Cellular Dna ◽  
In Cells

DNA base oxidation is considered to be a key event associated with disease initiation and progression in humans. Peroxyl radicals (ROO•) are important oxidants found in cells whose ability to react with the DNA bases has not been characterized extensively. In this paper, the products resulting from ROO• oxidation of the DNA bases are determined by gas chromatography/MS in comparison with authentic standards. ROO• radicals oxidize adenine and guanine to their 8-hydroxy derivatives, which are considered biomarkers of hydroxyl radical (HO•) oxidations in cells. ROO• radicals also oxidize adenine to its hydroxylamine, a previously unidentified product. ROO• radicals oxidize cytosine and thymine to the monohydroxy and dihydroxy derivatives that are formed by oxidative damage in cells. Identical ROO• oxidation profiles are observed for each base when exposed as deoxyribonucleosides, monohomopolymers and base-paired dihomopolymers. These results have significance for the development, utilization and interpretation of DNA base-derived biomarkers of oxidative damage associated with disease initiation and propagation, and support the idea that the mutagenic potential of N-oxidized bases, when generated in cellular DNA, will require careful evaluation. Adenine hydroxylamine is proposed as a specific molecular probe for the activity of ROO• in cellular systems.

scholarly journals Oxidation of Sperm DNA and Male Infertility

Antioxidants ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 97
Author(s):  
Leila Rashki Ghaleno ◽  
AliReza Alizadeh ◽  
Joël R. Drevet ◽  
Abdolhossein Shahverdi ◽  
Mojtaba Rezazadeh Valojerdi
Keyword(s):  
Oxidative Stress ◽  
Male Infertility ◽  
Oxidative Damage ◽  
Dna Fragmentation ◽  
Dna Bases ◽  
De Novo Mutation ◽  
Easy Access ◽  
Sperm Dna Fragmentation ◽  
Dna Base ◽  
Sperm Dna

One important reason for male infertility is oxidative stress and its destructive effects on sperm structures and functions. The particular composition of the sperm membrane, rich in polyunsaturated fatty acids, and the easy access of sperm DNA to oxidative damage due to sperm cell specific cytologic and metabolic features (no cytoplasm left and cells unable to mount stress responses) make it the cell type in metazoans most susceptible to oxidative damage. In particular, oxidative damage to the spermatozoa genome is an important issue and a cause of male infertility, usually associated with single- or double-strand paternal DNA breaks. Various methods of detecting sperm DNA fragmentation have become important diagnostic tools in the prognosis of male infertility and such assays are available in research laboratories and andrology clinics. However, to date, there is not a clear consensus in the community as to their respective prognostic value. Nevertheless, it is important to understand that the effects of oxidative stress on the sperm genome go well beyond DNA fragmentation alone. Oxidation of paternal DNA bases, particularly guanine and adenosine residues, the most sensitive residues to oxidative alteration, is the starting point for DNA damage in spermatozoa but is also a danger for the integrity of the embryo genetic material independently of sperm DNA fragmentation. Due to the lack of a spermatozoa DNA repair system and, if the egg is unable to correct the sperm oxidized bases, the risk of de novo mutation transmission to the embryo exists. These will be carried on to every cell of the future individual and its progeny. Thus, in addition to affecting the viability of the pregnancy itself, oxidation of the DNA bases in sperm could be associated with the development of conditions in young and future adults. Despite these important issues, sperm DNA base oxidation has not attracted much interest among clinicians due to the lack of simple, reliable, rapid and consensual methods of assessing this type of damage to the paternal genome. In addition to these technical issues, another reason explaining why the measurement of sperm DNA oxidation is not included in male fertility is likely to be due to the lack of strong evidence for its role in pregnancy outcome. It is, however, becoming clear that the assessment of DNA base oxidation could improve the efficiency of assisted reproductive technologies and provide important information on embryonic developmental failures and pathologies encountered in the offspring. The objective of this work is to review relevant research that has been carried out in the field of sperm DNA base oxidation and its associated genetic and epigenetic consequences.

scholarly journals Excision of Oxidatively Generated Guanine Lesions by Competitive DNA Repair Pathways

2021 ◽  
Vol 22 (5) ◽  
pp. 2698
Author(s):  
Vladimir Shafirovich ◽  
Nicholas E. Geacintov
Keyword(s):  
Excision Repair ◽  
Dna Lesions ◽  
Dna Templates ◽  
Circular Dna ◽  
Damage Sensing ◽  
Cell Extracts ◽  
Dna Base ◽  
Nucleotide Excision ◽  
Repair Pathways ◽  
Cellular Dna

The base and nucleotide excision repair pathways (BER and NER, respectively) are two major mechanisms that remove DNA lesions formed by the reactions of genotoxic intermediates with cellular DNA. It is generally believed that small non-bulky oxidatively generated DNA base modifications are removed by BER pathways, whereas DNA helix-distorting bulky lesions derived from the attack of chemical carcinogens or UV irradiation are repaired by the NER machinery. However, existing and growing experimental evidence indicates that oxidatively generated DNA lesions can be repaired by competitive BER and NER pathways in human cell extracts and intact human cells. Here, we focus on the interplay and competition of BER and NER pathways in excising oxidatively generated guanine lesions site-specifically positioned in plasmid DNA templates constructed by a gapped-vector technology. These experiments demonstrate a significant enhancement of the NER yields in covalently closed circular DNA plasmids (relative to the same, but linearized form of the same plasmid) harboring certain oxidatively generated guanine lesions. The interplay between the BER and NER pathways that remove oxidatively generated guanine lesions are reviewed and discussed in terms of competitive binding of the BER proteins and the DNA damage-sensing NER factor XPC-RAD23B to these lesions.

Prevention of Oxidative Damage to Cellular DNA by Mushroom-Derived Components

2001 ◽  
Vol 3 (2-3) ◽  
pp. 1 ◽  
Author(s):  
Yu-ling Shi ◽  
Anthony E. James ◽  
Iris F. F. Benzie ◽  
John A. Buswell
Keyword(s):  
Oxidative Damage ◽  
Cellular Dna

scholarly journals Endogenous oxidized DNA bases and APE1 regulate the formation of G-quadruplex structures in the genome

2020 ◽  
Vol 117 (21) ◽  
pp. 11409-11420 ◽  
Author(s):  
Shrabasti Roychoudhury ◽  
Suravi Pramanik ◽  
Hannah L. Harris ◽  
Mason Tarpley ◽  
Aniruddha Sarkar ◽  
...  
Keyword(s):  
Excision Repair ◽  
Factor Loading ◽  
Telomere Maintenance ◽  
Epigenetic Mechanism ◽  
Dna Bases ◽  
G Quadruplex ◽  
Base Excision ◽  
Ap Site ◽  
In Cells

Formation of G-quadruplex (G4) DNA structures in key regulatory regions in the genome has emerged as a secondary structure-based epigenetic mechanism for regulating multiple biological processes including transcription, replication, and telomere maintenance. G4 formation (folding), stabilization, and unfolding must be regulated to coordinate G4-mediated biological functions; however, how cells regulate the spatiotemporal formation of G4 structures in the genome is largely unknown. Here, we demonstrate that endogenous oxidized guanine bases in G4 sequences and the subsequent activation of the base excision repair (BER) pathway drive the spatiotemporal formation of G4 structures in the genome. Genome-wide mapping of occurrence of Apurinic/apyrimidinic (AP) site damage, binding of BER proteins, and G4 structures revealed that oxidized base-derived AP site damage and binding of OGG1 and APE1 are predominant in G4 sequences. Loss of APE1 abrogated G4 structure formation in cells, which suggests an essential role of APE1 in regulating the formation of G4 structures in the genome. Binding of APE1 to G4 sequences promotes G4 folding, and acetylation of APE1, which enhances its residence time, stabilizes G4 structures in cells. APE1 subsequently facilitates transcription factor loading to the promoter, providing mechanistic insight into the role of APE1 in G4-mediated gene expression. Our study unravels a role of endogenous oxidized DNA bases and APE1 in controlling the formation of higher-order DNA secondary structures to regulate transcription beyond its well-established role in safeguarding the genomic integrity.

scholarly journals The Protective Role of Sulfated Polysaccharides from Green Seaweed Udotea flabellum in Cells Exposed to Oxidative Damage

Marine Drugs ◽  
2018 ◽  
Vol 16 (4) ◽  
pp. 135 ◽  
Author(s):  
Fernando Presa ◽  
Maxsuell Marques ◽  
Rony Viana ◽  
Leonardo Nobre ◽  
Leandro Costa ◽  
...  
Keyword(s):  
Oxidative Damage ◽  
Protective Role ◽  
Sulfated Polysaccharides ◽  
Green Seaweed ◽  
In Cells

2′-(R)-Fluorinated mC, hmC, fC and caC triphosphates are substrates for DNA polymerases and TET-enzymes

2016 ◽  
Vol 52 (100) ◽  
pp. 14361-14364 ◽  
Author(s):  
A. S. Schröder ◽  
E. Parsa ◽  
K. Iwan ◽  
F. R. Traube ◽  
M. Wallner ◽  
...  
Keyword(s):  
Dna Polymerases ◽  
Dna Bases ◽  
Reaction Pathways ◽  
Tet Enzymes ◽  
In Cells

A deeper investigation of the chemistry that occurs on the newly discovered epigenetic DNA bases 5-hydroxymethyl-(hmdC), 5-formyl-(fdC), and 5-carboxy-deoxycytidine (cadC) requires chemical tool compounds, which are able to dissect the different potential reaction pathways in cells.

The Coffee Constituent Chlorogenic Acid Induces Cellular DNA Damage and Formation of Topoisomerase I– and II–DNA Complexes in Cells

2012 ◽  
Vol 60 (30) ◽  
pp. 7384-7391 ◽  
Author(s):  
Estefanía Burgos-Morón ◽  
José Manuel Calderón-Montaño ◽  
Manuel Luis Orta ◽  
Nuria Pastor ◽  
Concepción Pérez-Guerrero ◽  
...  
Keyword(s):  
Dna Damage ◽  
Chlorogenic Acid ◽  
Topoisomerase I ◽  
Dna Complexes ◽  
Cellular Dna ◽  
In Cells

scholarly journals Increased oxidative damage to all DNA bases in patients with type II diabetes mellitus

FEBS Letters ◽  
1999 ◽  
Vol 448 (1) ◽  
pp. 120-122 ◽  
Author(s):  
Almas Rehman ◽  
Jaffar Nourooz-Zadeh ◽  
Wenke Möller ◽  
Hans Tritschler ◽  
Paulo Pereira ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Oxidative Damage ◽  
Type Ii Diabetes ◽  
Type Ii Diabetes Mellitus ◽  
Dna Bases ◽  
Type Ii

scholarly journals Computational studies of DNA base repair mechanisms by nonheme iron dioxygenases: selective epoxidation and hydroxylation pathways

2020 ◽  
Vol 49 (14) ◽  
pp. 4266-4276
Author(s):  
Reza Latifi ◽  
Jennifer L. Minnick ◽  
Matthew G. Quesne ◽  
Sam P. de Visser ◽  
Laleh Tahsini
Keyword(s):  
Nonheme Iron ◽  
Dna Bases ◽  
Dft Study ◽  
Computational Studies ◽  
Repair Enzymes ◽  
Dna Base ◽  
Repair Mechanisms ◽  
High Valent

A detailed QM/MM and DFT study into the structure and reactivity of AlkB repair enzymes with alkylated DNA bases is reported. In particular, we investigate the aliphatic hydroxylation and CC epoxidation mechanisms of the enzymes by a high-valent iron(iv)–oxo intermediate.

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