Genomic integrity is constantly challenged by DNA damaging agents such as reactive oxygen species (ROS). Consequently, DNA damage can compromise the fidelity and efficiency of essential DNA metabolic processes, including replication and transcription, which may contribute significantly to the etiology of many human diseases. Here, we review one family of DNA lesions, the epimeric 2-deoxyribose lesions, which arise from the improper chemical repair of the 2-deoxyribose radicals. Unlike most other DNA lesions, the epimeric 2-deoxyribose lesions are indistinguishable from their corresponding unmodified nucleosides in both molecular mass and chemical reactivity. We placed our emphasis of discussion on the formation of these lesions, their impact on the structure and stability of duplex DNA, their biological consequences, their potential therapeutic relevance, and future research directions about these modified nucleosides.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4002128 | PMC |
| http://dx.doi.org/10.1021/tx400430g | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The L-Rhamnose Biosynthetic Pathway in : Identification and Characterization of UDP-D-Glucose 4,6-dehydratase.
Int J Mol Sci
November 2022
Department of Experimental Medicine, University of Genova, 16132 Genova, Italy.
is the causative agent of one of the most widespread sexually transmitted diseases in the world. The adhesion of the parasite to the vaginal epithelial cells is mediated by specific proteins and by a complex glycan structure, the lipoglycan (TvLG), which covers the pathogen surface. L-rhamnose is an important component of TvLG, comprising up to 40% of the monosaccharides.
View Article and Find Full Text PDFCytotoxic and Mutagenic Properties of C1' and C3'-Epimeric Lesions of 2'-Deoxyribonucleosides in Human Cells.
ACS Chem Biol
March 2019
Department of Chemistry , University of California, Riverside , California 92521-0403 , United States.
Genomic integrity is constantly challenged by exposure to environmental and endogenous genotoxic agents. Reactive oxygen species (ROS) represent one of the most common types of DNA damaging agents. While ROS mainly induce single-nucleobase lesions, epimeric 2-deoxyribose lesions can also be induced upon hydrogen atom abstraction from the C1', C3', or C4' carbon and the subsequent incorrect chemical repair of the resulting carbon-centered radicals.
View Article and Find Full Text PDFConfigurational and Conformational Equilibria of N-(2-Deoxy-d-erythro-pentofuranosyl)-2,6-diamino-3,4-dihydro-4-oxo-5- N-methylformamidopyrimidine (MeFapy-dG) Lesion in DNA.
Chem Res Toxicol
September 2018
Department of Chemistry , Vanderbilt UniversityCenter for Structural Biology, Vanderbilt Center in Molecular Toxicology, and the Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville , Tennessee 37235 , United States.
The most common lesion in DNA occurring due to clinical treatment with Temozolomide or cellular exposures to other methylating agents is 7-methylguanine (N7-Me-dG). It can undergo a secondary reaction to form N-(2-deoxy-d-erythro-pentofuranosyl)-2,6-diamino-3,4-dihydro-4-oxo-5- N-methylformamidopyrimidine (MeFapy-dG). MeFapy-dG undergoes epimerization in DNA to produce either α or β deoxyribose anomers.
View Article and Find Full Text PDFCytotoxic and Mutagenic Properties of C3'-Epimeric Lesions of 2'-Deoxyribonucleosides in Escherichia coli Cells.
Biochemistry
July 2017
Environmental Toxicology Graduate Program and ‡Department of Chemistry, University of California, Riverside, California 92521-0403, United States.
Reactive oxygen species (ROS), resulting from endogenous metabolism and/or environmental exposure, can induce damage to the 2-deoxyribose moiety in DNA. Specifically, a hydrogen atom from each of the five carbon atoms in 2-deoxyribose can be abstracted by hydroxyl radical, and improper chemical repair of the ensuing radicals formed at the C1', C3', and C4' positions can lead to the stereochemical inversion at these sites to yield epimeric 2-deoxyribose lesions. Although ROS-induced single-nucleobase lesions have been well studied, the biological consequences of the C3'-epimeric lesions of 2'-deoxynucleosides, i.
View Article and Find Full Text PDFIn vivo detection and replication studies of α-anomeric lesions of 2'-deoxyribonucleosides.
Nucleic Acids Res
September 2015
Department of Chemistry, University of California, Riverside, CA 92521, USA
DNA damage, arising from endogenous metabolism or exposure to environmental agents, may perturb the transmission of genetic information by blocking DNA replication and/or inducing mutations, which contribute to the development of cancer and likely other human diseases. Hydroxyl radical attack on the C1', C3' and C4' of 2-deoxyribose can give rise to epimeric 2-deoxyribose lesions, for which the in vivo occurrence and biological consequences remain largely unexplored. Through independent chemical syntheses of all three epimeric lesions of 2'-deoxyguanosine (dG) and liquid chromatography-tandem mass spectrometry analysis, we demonstrated unambiguously the presence of substantial levels of the α-anomer of dG (α-dG) in calf thymus DNA and in DNA isolated from mouse pancreatic tissues.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!