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DNA, Volume 3, Issue 2 (June 2023) – 5 articles

Cover Story (view full-size image): Oxime carbamates are known commercial pesticides. The easy photo homolysis of their N-O vulnerable bond creates amine and imine radicals, which seem to efficiently cause DNA photocleavage, interestingly, with high specificity, when a carbamate linker has p-Cl-Ph moiety. Irradiations such as UVB and UVA emitted by sunlight can be absorbed by most aromatic derivatives. Using artificial UVB/UVA light, DNA photocleavage has been observed at low concentrations of the compounds. The 3-NO2-Ph-carbamidoxime-related carbamoyl ester showed pesticidal activity against Bemisia tabaci, which is one of the most devastating pests of numerous crops worldwide. A qualitative test revealed a moderate specificity against the adult population, whereas it was almost zero in the absence of UVA irradiation. View this paper
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10 pages, 1540 KiB  
Article
Identification of Proteins Specifically Assembled on a Stem-Loop Composed of a CAG Triplet Repeat
by Robert P. Fuchs, Asako Isogawa, Joao A. Paulo and Shingo Fujii
DNA 2023, 3(2), 109-118; https://doi.org/10.3390/dna3020009 - 6 Jun 2023
Viewed by 1580
Abstract
Human genomic DNA contains a number of diverse repetitive sequence motifs, often identified as fragile sites leading to genetic instability. Among them, expansion events occurring at triplet repeats have been extensively studied due to their association with neurological disorders, including Huntington’s disease (HD). [...] Read more.
Human genomic DNA contains a number of diverse repetitive sequence motifs, often identified as fragile sites leading to genetic instability. Among them, expansion events occurring at triplet repeats have been extensively studied due to their association with neurological disorders, including Huntington’s disease (HD). In the case of HD, expanded CAG triplet repeats in the HTT gene are thought to cause the onset. The expansion of CAG triplet repeats is believed to be triggered by the emergence of stem-loops composed of CAG triplet repeats, while the underlying molecular mechanisms are largely unknown. Therefore, identifying proteins recruited on such stem loops would be useful to understand the molecular mechanisms leading to the genetic instability of CAG triplet repeats. We previously developed a plasmid DNA pull-down methodology that captures proteins specifically assembled on any sequence of interest using nuclear extracts. Analysis by Mass Spectrometry revealed that among the proteins specifically bound to a stem-loop composed of CAG triplet repeats, many turned out to belong to DNA repair pathways. We expect our data set to represent a useful entry point for the design of assays allowing the molecular mechanisms of genetic instability at CAG triplet repeats to be explored. Full article
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5 pages, 188 KiB  
Opinion
Preimplantation Testing for Polygenic Disease (PGT-P): Brave New World or Mad Pursuit?
by Darren K. Griffin and Anthony T. Gordon
DNA 2023, 3(2), 104-108; https://doi.org/10.3390/dna3020008 - 10 May 2023
Cited by 2 | Viewed by 2971
Abstract
In preimplantation testing for monogenic disease (PGT-M), we are used to specific and directed diagnoses. Preimplantation testing for polygenic disease (PGT-P), however, represents a further level of complexity in that multiple genes are tested for with an associated polygenic risk score (PRS), usually [...] Read more.
In preimplantation testing for monogenic disease (PGT-M), we are used to specific and directed diagnoses. Preimplantation testing for polygenic disease (PGT-P), however, represents a further level of complexity in that multiple genes are tested for with an associated polygenic risk score (PRS), usually established by a genome-wide association study (GWAS). PGT-P has a series of pros and cons and, like many areas of genetics in reproductive medicine, there are vocal proponents and opponents on both sides. As with all things, the question needs to be asked, how much benefit does PGT-P provide in comparison to the risks involved? For each disease, a case will need to be made for PGT-P, as will a justification that the family involved will actually benefit; the worry is that this might be more work than the cost justifies. Full article
(This article belongs to the Special Issue In Memoriam of Joy Dorothy Ann Delhanty)
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3 pages, 173 KiB  
Editorial
From Mutation and Repair to Therapeutics
by Ashis Basu and Deyu Li
DNA 2023, 3(2), 101-103; https://doi.org/10.3390/dna3020007 - 27 Apr 2023
Viewed by 1074
Abstract
As DNA research has developed, in this Special Issue of DNA, we aimed to explore recent advancements, with an emphasis on the DNA damage-induced alteration of cellular functions [...] Full article
(This article belongs to the Special Issue From Mutation and Repair to Therapeutics)
16 pages, 2480 KiB  
Article
Exploration of the DNA Photocleavage Activity of O-Halo-phenyl Carbamoyl Amidoximes: Studies of the UVA-Induced Effects on a Major Crop Pest, the Whitefly Bemisia tabaci
by Anastasios Panagopoulos, Konstantina Alipranti, Kyriaki Mylona, Polinikis Paisidis, Stergios Rizos, Alexandros E. Koumbis, Emmanouil Roditakis and Konstantina C. Fylaktakidou
DNA 2023, 3(2), 85-100; https://doi.org/10.3390/dna3020006 - 4 Apr 2023
Cited by 1 | Viewed by 1604
Abstract
The DNA photocleavage effect of halogenated O-carbamoyl derivatives of 4-MeO-benzamidoxime under UVB and UVA irradiation was studied in order to identify the nature, position, and number of halogens on the carbamoyl moiety that ensure photoactivity. F, Cl, and Br-phenyl carbamate esters (PCME) [...] Read more.
The DNA photocleavage effect of halogenated O-carbamoyl derivatives of 4-MeO-benzamidoxime under UVB and UVA irradiation was studied in order to identify the nature, position, and number of halogens on the carbamoyl moiety that ensure photoactivity. F, Cl, and Br-phenyl carbamate esters (PCME) exhibited activity with the p-Cl-phenyl derivative to show excellent photocleavage against pBR322 plasmid DNA. m-Cl-PCME has diminished activity, whereas the presence of two halogen atoms reduced DNA photocleavage. The substitution on the benzamidoxime scaffold was irrelevant to the activity. The mechanism of action indicated function in the absence of oxygen, probably via radicals derived from the N-O bond homolysis of the carbamates and in air via hydroxyl radicals and partially singlet oxygen. The UVA-vis area of absorption of the nitro-benzamidoxime p-Cl-PCMEs allowed for the investigation of their potential efficacy as photopesticides under UVA irradiation against the whitefly Bemisia tabaci, a major pest of numerous crops. The m-nitro derivative exhibited a moderate specificity against the adult population. Nymphs were not affected. The compound was inactive in the dark. This result may allow for the development of lead compounds for the control of agricultural insect pests that can cause significant economic damage in crop production. Full article
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20 pages, 719 KiB  
Review
Kinetic Studies on the 2-Oxoglutarate/Fe(II)-Dependent Nucleic Acid Modifying Enzymes from the AlkB and TET Families
by Zhiyuan Peng, Jian Ma, Christo Z. Christov, Tatyana Karabencheva-Christova, Nicolai Lehnert and Deyu Li
DNA 2023, 3(2), 65-84; https://doi.org/10.3390/dna3020005 - 30 Mar 2023
Cited by 2 | Viewed by 2357
Abstract
Nucleic acid methylations are important genetic and epigenetic biomarkers. The formation and removal of these markers is related to either methylation or demethylation. In this review, we focus on the demethylation or oxidative modification that is mediated by the 2-oxoglutarate (2-OG)/Fe(II)-dependent AlkB/TET family [...] Read more.
Nucleic acid methylations are important genetic and epigenetic biomarkers. The formation and removal of these markers is related to either methylation or demethylation. In this review, we focus on the demethylation or oxidative modification that is mediated by the 2-oxoglutarate (2-OG)/Fe(II)-dependent AlkB/TET family enzymes. In the catalytic process, most enzymes oxidize 2-OG to succinate, in the meantime oxidizing methyl to hydroxymethyl, leaving formaldehyde and generating demethylated base. The AlkB enzyme from Escherichia coli has nine human homologs (ALKBH1-8 and FTO) and the TET family includes three members, TET1 to 3. Among them, some enzymes have been carefully studied, but for certain enzymes, few studies have been carried out. This review focuses on the kinetic properties of those 2-OG/Fe(II)-dependent enzymes and their alkyl substrates. We also provide some discussions on the future directions of this field. Full article
(This article belongs to the Special Issue From Mutation and Repair to Therapeutics)
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