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8-OxodG: A Potential Biomarker for Chronic Oxidative Stress Induced by High-LET Radiation. 8-OxodG：高放电辐射诱发慢性氧化应激的潜在生物标志物

DNA Pub Date : 2024-09-01 Epub Date: 2024-08-01 DOI: 10.3390/dna4030015

Kamendra Kumar, Albert J Fornace, Shubhankar Suman

{"title":"8-OxodG: A Potential Biomarker for Chronic Oxidative Stress Induced by High-LET Radiation.","authors":"Kamendra Kumar, Albert J Fornace, Shubhankar Suman","doi":"10.3390/dna4030015","DOIUrl":"https://doi.org/10.3390/dna4030015","url":null,"abstract":"Oxidative stress-mediated biomolecular damage is a characteristic feature of ionizing radiation (IR) injury, leading to genomic instability and chronic health implications. Specifically, a dose- and linear energy transfer (LET)-dependent persistent increase in oxidative DNA damage has been reported in many tissues and biofluids months after IR exposure. Contrary to low-LET photon radiation, high-LET IR exposure is known to cause significantly higher accumulations of DNA damage, even at sublethal doses, compared to low-LET IR. High-LET IR is prevalent in the deep space environment (i.e., beyond Earth's magnetosphere), and its exposure could potentially impair astronauts' health. Therefore, the development of biomarkers to assess and monitor the levels of oxidative DNA damage can aid in the early detection of health risks and would also allow timely intervention. Among the recognized biomarkers of oxidative DNA damage, 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-OxodG) has emerged as a promising candidate, indicative of chronic oxidative stress. It has been reported to exhibit differing levels following equivalent doses of low- and high-LET IR. This review discusses 8-OxodG as a potential biomarker of high-LET radiation-induced chronic stress, with special emphasis on its potential sources, formation, repair mechanisms, and detection methods. Furthermore, this review addresses the pathobiological implications of high-LET IR exposure and its association with 8-OxodG. Understanding the association between high-LET IR exposure-induced chronic oxidative stress, systemic levels of 8-OxodG, and their potential health risks can provide a framework for developing a comprehensive health monitoring biomarker system to safeguard the well-being of astronauts during space missions and optimize long-term health outcomes.","PeriodicalId":72835,"journal":{"name":"DNA","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11391509/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142302463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Origin of Type II tRNA Variable Loops, Aminoacyl-tRNA Synthetase Allostery from Distal Determinants, and Diversification of Life 第二类 tRNA 可变环的起源、来自远端决定因素的氨基酰-tRNA 合成酶异构体以及生命的多样化

DNA Pub Date : 2024-08-09 DOI: 10.3390/dna4030017

Lei Lei, Zachary Frome Burton

{"title":"Origin of Type II tRNA Variable Loops, Aminoacyl-tRNA Synthetase Allostery from Distal Determinants, and Diversification of Life","authors":"Lei Lei, Zachary Frome Burton","doi":"10.3390/dna4030017","DOIUrl":"https://doi.org/10.3390/dna4030017","url":null,"abstract":"The three 31 nucleotide minihelix tRNA evolution theorem describes the evolution of type I and type II tRNAs to the last nucleotide. In databases, type I and type II tRNA V loops (V for variable) were improperly aligned, but alignment based on the theorem is accurate. Type II tRNA V arms were a 3′-acceptor stem (initially CCGCCGC) ligated to a 5′-acceptor stem (initially GCGGCGG). The type II V arm evolved to form a stem–loop–stem. In Archaea, tRNALeu and tRNASer are type II. In Bacteria, tRNALeu, tRNASer, and tRNATyr are type II. The trajectory of the type II V arm is determined by the number of unpaired bases just 5′ of the Levitt base (Vmax). For Archaea, tRNALeu has two unpaired bases, and tRNASer has one unpaired base. For Bacteria, tRNATyr has two unpaired bases, tRNALeu has one unpaired base, and tRNASer has zero unpaired bases. Thus, the number of synonymous type II tRNA sets is limited by the possible trajectory set points of the arm. From the analysis of aminoacyl-tRNA synthetase structures, contacts to type II V arms appear to adjust allosteric tension communicated primarily via tRNA to aminoacylating and editing active sites. To enhance allostery, it appears that type II V arm end loop contacts may tend to evolve to V arm stem contacts.","PeriodicalId":72835,"journal":{"name":"DNA","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141921730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Comparative Analysis of Five Forensic PCR Kits in Duplets 五种法医 PCR 检测试剂盒的双联对比分析

DNA Pub Date : 2024-07-11 DOI: 10.3390/dna4030014

Tamás Cseppentő, Norbert G. Valis, G. Bárány, Bálint Megadja, Attila Heinrich, Nóra M. Magonyi

{"title":"Comparative Analysis of Five Forensic PCR Kits in Duplets","authors":"Tamás Cseppentő, Norbert G. Valis, G. Bárány, Bálint Megadja, Attila Heinrich, Nóra M. Magonyi","doi":"10.3390/dna4030014","DOIUrl":"https://doi.org/10.3390/dna4030014","url":null,"abstract":"In forensic DNA laboratories, it is important to conduct internal validations of the commercially available kits of short tandem repeat (STR) loci and to investigate their individual and combined effectiveness. This study aims to report on a comparative investigation of the forensic kits used in our laboratory and their combinations in analysing low-copy-number (LCN) human DNA samples. We used five partly overlapping multiplex kits with different marker configurations from different manufacturers: the NGM SelectTM PCR Amplification Kit, NGM DetectTM, the GlobalFilerTM Amplification Kit (Applied BiosystemTM, Foster City, CA, USA), the PowerPlex® Fusion 6C System (Promega Co., Madison, WI, USA) and the Investigator® 24plex QS Kit (Qiagen GmbH, Hilden, Germany). The efficacy of the kits was scrutinised by specific criteria, such as allelic dropout rate, the individually calculated Likelihood Ratio (LR) of consensus profiles and the LR value of the composite profile produced by the combined profiles of two kits. According to the results, the pairing of PowerPlex® Fusion 6C System and Investigator® 24plex QS produced the lowest, while the pairing of the NGM DetectTM and GlobalFilerTM kits provided the highest LR value. In summary, our study is meant to aid the selection of the optimal kit combination for samples of different qualities.","PeriodicalId":72835,"journal":{"name":"DNA","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141655580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Efficient Elimination of mtDNA from Mammalian Cells with 2′,3′-Dideoxycytidine 用 2′,3′-二脱氧胞苷高效消除哺乳动物细胞中的 mtDNA

DNA Pub Date : 2024-07-04 DOI: 10.3390/dna4030013

N. Kozhukhar, Mikhail F. Alexeyev

{"title":"Efficient Elimination of mtDNA from Mammalian Cells with 2′,3′-Dideoxycytidine","authors":"N. Kozhukhar, Mikhail F. Alexeyev","doi":"10.3390/dna4030013","DOIUrl":"https://doi.org/10.3390/dna4030013","url":null,"abstract":"Mammalian cell lines devoid of mitochondrial DNA (mtDNA) are indispensable in studies aimed at elucidating the contribution of mtDNA to various cellular processes or interactions between nuclear and mitochondrial genomes. However, the repertoire of tools for generating such cells (also known as rho-0 or ρ0 cells) remains limited, and approaches remain time- and labor-intensive, ultimately limiting their availability. Ethidium bromide (EtBr), which is most commonly used to induce mtDNA loss in mammalian cells, is cytostatic and mutagenic as it affects both nuclear and mitochondrial genomes. Therefore, there is growing interest in new tools for generating ρ0 cell lines. Here, we examined the utility of 2′,3′-dideoxycytidine (ddC, zalcitabine) alone or in combination with EtBr for generating ρ0 cell lines of mouse and human origin as well as inducing the ρ0 state in mouse/human somatic cell hybrids. We report that ddC is superior to EtBr in both immortalized mouse fibroblasts and human 143B cells. Also, unlike EtBr, ddC exhibits no cytostatic effects at the highest concentration tested (200 μM), making it more suitable for general use. We conclude that ddC is a promising new tool for generating mammalian ρ0 cell lines.","PeriodicalId":72835,"journal":{"name":"DNA","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141677781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Child Telomere Length at 11–12 Years of Age Is Not Associated with Pregnancy Complications 11-12 岁儿童端粒长度与妊娠并发症无关

DNA Pub Date : 2024-06-11 DOI: 10.3390/dna4020011

T. Bianco-Miotto, Sadia Hossain, Nahal Habibi, Dandara G. Haag, J. Grieger

{"title":"Child Telomere Length at 11–12 Years of Age Is Not Associated with Pregnancy Complications","authors":"T. Bianco-Miotto, Sadia Hossain, Nahal Habibi, Dandara G. Haag, J. Grieger","doi":"10.3390/dna4020011","DOIUrl":"https://doi.org/10.3390/dna4020011","url":null,"abstract":"Children born from pregnancy complications are at higher risk of chronic diseases in adulthood. Identifying which children born from a complicated pregnancy are likely to suffer from later chronic disease is important in order to intervene to prevent or delay the onset of disease. This study examined the associations between the major pregnancy complications (gestational diabetes, high blood pressure, small- and large for gestational age, and preterm birth) and child telomere length, a biomarker of chronic disease risk. This was a population-based longitudinal analysis using data from the Longitudinal Study of Australian Children. The primary outcome is telomere length, measured in 11–12-year-old children. Multivariable linear regression was used to estimate the association between pregnancy complications and child telomere length, adjusting for a range of a priori confounders. Data from 841 families were used. One in four pregnancies (27.1%) featured a pregnancy complication. In the adjusted analysis, there was no association between pregnancy complications and child telomere length (high blood pressure: mean difference (95% CI): 0.00 (−0.12, 0.12); gestational diabetes (0.05 (−0.10, 0.19)); small for gestational age (0.07 (−0.04, 0.19)); large for gestational age (−0.06 (−0.15, 0.03)); and preterm birth (−0.10 (−0.21, 0.01)). Our results do not support the notion that telomere length is shorter in children born to mothers after a pregnancy complication. Methodological considerations should be rigorous to improve the reproducibility of findings.","PeriodicalId":72835,"journal":{"name":"DNA","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141356306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Transposon and Transgene Tribulations in Mosquitoes: A Perspective of piRNA Proportions. 蚊子中的转座子和转基因磨难：piRNA 比例透视。

DNA Pub Date : 2024-06-01 Epub Date: 2024-03-30 DOI: 10.3390/dna4020006

Nelson C Lau, Vanessa M Macias

{"title":"Transposon and Transgene Tribulations in Mosquitoes: A Perspective of piRNA Proportions.","authors":"Nelson C Lau, Vanessa M Macias","doi":"10.3390/dna4020006","DOIUrl":"10.3390/dna4020006","url":null,"abstract":"Mosquitoes, like Drosophila, are dipterans, the order of \"true flies\" characterized by a single set of two wings. Drosophila are prime model organisms for biomedical research, while mosquito researchers struggle to establish robust molecular biology in these that are arguably the most dangerous vectors of human pathogens. Both insects utilize the RNA interference (RNAi) pathway to generate small RNAs to silence transposons and viruses, yet details are emerging that several RNAi features are unique to each insect family, such as how culicine mosquitoes have evolved extreme genomic feature differences connected to their unique RNAi features. A major technical difference in the molecular genetic studies of these insects is that generating stable transgenic animals are routine in Drosophila but still variable in stability in mosquitoes, despite genomic DNA-editing advances. By comparing and contrasting the differences in the RNAi pathways of Drosophila and mosquitoes, in this review we propose a hypothesis that transgene DNAs are possibly more intensely targeted by mosquito RNAi pathways and chromatin regulatory pathways than in Drosophila. We review the latest findings on mosquito RNAi pathways, which are still much less well understood than in Drosophila, and we speculate that deeper study into how mosquitoes modulate transposons and viruses with Piwi-interacting RNAs (piRNAs) will yield clues to improving transgene DNA expression stability in transgenic mosquitoes.","PeriodicalId":72835,"journal":{"name":"DNA","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11286205/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141794184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mutagenesis and Repair of γ-Radiation- and Radical-Induced Tandem DNA Lesions γ-射线和辐射诱导的串联 DNA 病变的突变和修复

DNA Pub Date : 2024-05-06 DOI: 10.3390/dna4020009

A. Basu, Laureen C. Colis, J. H. T. Bacurio

引用次数: 0

Exploring the Roles of Different DNA Repair Proteins in Short Inverted Repeat Mediated Genomic Instability: A Pilot Study 探索不同 DNA 修复蛋白在短倒位重复介导的基因组不稳定性中的作用：一项试点研究

DNA Pub Date : 2024-04-05 DOI: 10.3390/dna4020008

Pooja Mandke, Karen M. Vasquez

{"title":"Exploring the Roles of Different DNA Repair Proteins in Short Inverted Repeat Mediated Genomic Instability: A Pilot Study","authors":"Pooja Mandke, Karen M. Vasquez","doi":"10.3390/dna4020008","DOIUrl":"https://doi.org/10.3390/dna4020008","url":null,"abstract":"Repetitive DNA sequences are abundant in the human genome and can adopt alternative (i.e., non-B) DNA structures. These sequences contribute to diverse biological functions, including genomic instability. Previously, we found that Z-DNA-, H-DNA- and cruciform DNA-forming sequences are mutagenic, implicating them in cancer etiology. These sequences can stimulate the formation of DNA double-strand breaks (DSBs), causing deletions via cleavage by the endonuclease ERCC1-XPF. Interestingly, the activity of ERCC1-XPF in H-DNA-induced mutagenesis is nucleotide excision repair (NER)-dependent, but its role in Z-DNA-induced mutagenesis is NER-independent. Instead, Z-DNA is processed by ERCC1-XPF in a mechanism dependent on the mismatch repair (MMR) complex, MSH2-MSH3. These observations indicate distinct mechanisms of non-B-induced genomic instability. However, the roles of NER and MMR proteins, as well as additional nucleases (CtIP and MRE11), in the processing of cruciform DNA remain unknown. Here, we present data on the processing of cruciform-forming short inverted repeats (IRs) by DNA repair proteins using mammalian cell-based systems. From this pilot study, we show that, in contrast to H-DNA and Z-DNA, short IRs are processed in a NER- and MMR-independent manner, and the nucleases CtIP and MRE11 suppress short IR-induced genomic instability in mammalian cells.","PeriodicalId":72835,"journal":{"name":"DNA","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140738358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Activity and Silencing of Transposable Elements in C. elegans 秀丽隐杆线虫中可转座元件的活性与沉默

DNA Pub Date : 2024-04-02 DOI: 10.3390/dna4020007

Sylvia E. J. Fischer

{"title":"Activity and Silencing of Transposable Elements in C. elegans","authors":"Sylvia E. J. Fischer","doi":"10.3390/dna4020007","DOIUrl":"https://doi.org/10.3390/dna4020007","url":null,"abstract":"Since the discovery of transposable elements (TEs) in maize in the 1940s by Barbara McClintock transposable elements have been described as junk, as selfish elements with no benefit to the host, and more recently as major determinants of genome structure and genome evolution. TEs are DNA sequences that are capable of moving to new sites in the genome and making additional copies of themselves while doing so. To limit the propagation of TEs, host silencing mechanisms are directed at transposon-encoded genes that are required for mobilization. The mutagenic properties of TEs, the potential of TEs to form new genes and affect gene expression, together with the host silencing mechanisms, shape eukaryotic genomes and drive genome evolution. While TEs constitute more than half of the genome in many higher eukaryotes, transposable elements in the nematode C. elegans form a relatively small proportion of the genome (approximately 15%). Genetic studies of transposon silencing, and the discovery of RNA interference (RNAi) in C. elegans, propelled Caenorhabditis elegans (C. elegans) to the forefront of studies of RNA-based mechanisms that silence TEs. Here, I will review the transposable elements that are present and active in the C. elegans genome, and the host defense mechanisms that silence these elements.","PeriodicalId":72835,"journal":{"name":"DNA","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140751207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

How Chromatin Motor Complexes Influence the Nuclear Architecture: A Review of Chromatin Organization, Cohesins, and Condensins with a Focus on C. elegans 染色质马达复合物如何影响核结构？染色质组织、聚合素和凝集素综述（以秀丽隐杆线虫为重点

DNA Pub Date : 2024-03-11 DOI: 10.3390/dna4010005

Bahaar Chawla, G. Csankovszki

引用次数: 0