It has been shown that in addition to formation of pyrimidine dimers, UV irradiation of DNA in the absence of photosensitizer also induces formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine, but the mechanism of formation of that oxidized base has not been clearly established. In the present study, we provide an unambiguous demonstration that absorption of UVC and UVB radiation by the nucleobases induces DNA oxidation via a direct process (one-electron oxidation) and not singlet oxygen. Evidence arose from the fact that polyamine-guanine adducts that are specifically produced through the transient formation of guanine radical cation are generated following UV irradiation of DNA in the presence of a polyamine even in the absence of any photosensitizer.
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http://dx.doi.org/10.1021/acs.jpclett.6b01781 | DOI Listing |
Chem Res Toxicol
December 2024
University of Missouri, Department of Chemistry, 125 Chemistry Building, Columbia, Missouri 65211, United States.
Apurinic/apyrimidinic endonuclease 1 (APE1) is a central enzyme in the base excision repair (BER) pathway. APE1 catalyzes incision of the phosphodiester linkage on the 5'-side of apurinic/apyrimidinic (AP) sites during the repair of damaged nucleobases in cellular DNA. Inhibition of this enzyme can potentiate the action of DNA-damaging chemotherapeutic agents.
View Article and Find Full Text PDFAnal Chem
December 2024
Department of Occupational and Environmental Health, School of Public Health, Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China.
5-Methylcytosine (5mC) is the most significant DNA modification present in mammalian genomes. Understanding the roles of 5mC in diverse biological processes requires quantitative detection at single-base resolution. In this study, we engineered the repressor of the silencing 1 (ROS1) protein derived from to enhance its 5mC glycosylase/lyase activity, resulting in the creation of the engineered ROS1 (eROS1) protein.
View Article and Find Full Text PDFJ Photochem Photobiol B
December 2024
Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André, São Paulo, SP 09210-580, Brazil.
In this review, we compare the mechanisms and consequences of electronic excitation of DNA via photon absorption or photosensitization, as well as by chemically induced generation of excited states. The absorption of UV radiation by DNA is known to produce cyclobutane pyrimidine dimers (CPDs) and thymine pyrimidone photoproducts. Photosensitizers are known to enable such transformations using UV-A and visible light by generating triplet species able to transfer energy to DNA.
View Article and Find Full Text PDFChem Res Toxicol
December 2024
Department of Medical Imaging and Radiation Sciences, Faculty of Medicine and Health Sciences, Université de Sherbrooke, 3001, 12e Avenue Nord, Sherbrooke, Québec J1H 5N4, Canada.
Radical oxidation of DNA gives rise to potentially deleterious lesions such as strand breaks and various nucleobase modifications including 5-formyl-2'-deoxyuridine (5-fo-dU), a prevalent product derived from the oxidation of the C5-methyl group of thymidine. The present study investigates the unusual transformation of 5-fo-dU into 5-hydroxy-2'-deoxyuridine (5-oh-dU) and 5,6-dihydroxy-5,6-dihydro-2'-deoxuridine (gly-dU), two products typically associated with the oxidation of 2'-deoxycytidine. Detailed mechanistic analyses reveal that hydrogen peroxide, either generated as a byproduct of ascorbate autoxidation or added exogenously, mediates the formation of these oxidatively induced C5-dealkylated products.
View Article and Find Full Text PDFJ Mol Model
November 2024
Sevastopol State University, Universitetskaya Str., 33, Crimea, 299053, Sevastopol, Ukraine.
Context: In this work, we are the first to perform a theoretical analysis of photoinduced charge transfer in the intercalation complex of thionine (TH) with double-stranded DNA, which was observed in experiments. Efficient DNA binding and long-wave absorption maximum make TH an attractive photosensitizer. d(CpG) tetranucleotide was used as a minimal model DNA fragment.
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