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DNA glycosylases

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https://www.readbyqxmd.com/read/29348879/loss-of-neil3-dna-glycosylase-markedly-increases-replication-associated-double-strand-breaks-and-enhances-sensitivity-to-atr-inhibitor-in-glioblastoma-cells
#1
Alex W Klattenhoff, Megha Thakur, Christopher S Chu, Debolina Ray, Samy L Habib, Dawit Kidane
DNA endonuclease eight-like glycosylase 3 (NEIL3) is one of the DNA glycosylases that removes oxidized DNA base lesions from single-stranded DNA (ssDNA) and non-B DNA structures. Approximately seven percent of human tumors have an altered NEIL3 gene. However, the role of NEIL3 in replication-associated repair and its impact on modulating treatment response is not known. Here, we report that NEIL3 is localized at the DNA double-strand break (DSB) sites during oxidative DNA damage and replication stress. Loss of NEIL3 significantly increased spontaneous replication-associated DSBs and recruitment of replication protein A (RPA)...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29341606/hogg1-removes-solution-accessible-8-oxog-lesions-from-globally-substituted-nucleosomes-except-at-the-dyad-region
#2
Katharina Bilotti, Mary E Tarantino, Sarah Delaney
Persistent DNA damage is responsible for mutagenesis, aging, and disease. Repair of the prototypic oxidatively damaged guanine lesion 8-oxo-7,8-dihydroguanine (8-oxoG) is initiated by oxoguanine glycosylase (hOGG1 in humans). In this work, we examine hOGG1 activity on DNA packaged as it is in chromatin, in a nucleosome core particle (NCP). We use synthetic methods to generate a population of NCPs with G to 8-oxoG substitutions and evaluate the global profile of hOGG1 repair in packaged DNA. For several turns of the helix, we observe that solution-accessible 8-oxoG are sites of activity for hOGG1...
January 17, 2018: Biochemistry
https://www.readbyqxmd.com/read/29339505/nonenzymatic-release-of-n7-methylguanine-channels-repair-of-abasic-sites-into-an-ap-endonuclease-independent-pathway-in-arabidopsis
#3
Casimiro Barbado, Dolores Córdoba-Cañero, Rafael R Ariza, Teresa Roldán-Arjona
Abasic (apurinic/apyrimidinic, AP) sites in DNA arise from spontaneous base loss or by enzymatic removal during base excision repair. It is commonly accepted that both classes of AP site have analogous biochemical properties and are equivalent substrates for AP endonucleases and AP lyases, although the relative roles of these two types of enzymes are not well understood. We provide here genetic and biochemical evidence that, in Arabidopsis, AP sites generated by spontaneous loss of N7-methylguanine (N7-meG) are exclusively repaired through an AP endonuclease-independent pathway initiated by FPG, a bifunctional DNA glycosylase with AP lyase activity...
January 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29336305/inferring-joint-sequence-structural-determinants-of-protein-functional-specificity
#4
Andrew F Neuwald, L Aravind, Stephen F Altschul
Residues responsible for allostery, cooperativity, and other subtle but functionally important interactions remain difficult to detect. To aid such detection, we employ statistical inference based on the assumption that residues distinguishing a protein subgroup from evolutionarily divergent subgroups often constitute an interacting functional network. We identify such networks with the aid of two measures of statistical significance. One measure aids identification of divergent subgroups based on distinguishing residue patterns...
January 16, 2018: ELife
https://www.readbyqxmd.com/read/29335541/modulation-of-uvb-induced-carcinogenesis-by-activation-of-alternative-dna-repair-pathways
#5
Yan Sha, Vladimir Vartanian, Nichole Owen, Stephanie J Mengden Koon, Marcus J Calkins, Courtney S Thompson, Zahra Mirafzali, Sara Mir, Lisa E Goldsmith, Huaping He, Chun Luo, Scott M Brown, Paul W Doetsch, Andy Kaempf, Jeong Y Lim, Amanda K McCullough, R Stephen Lloyd
The molecular basis for ultraviolet (UV) light-induced nonmelanoma and melanoma skin cancers centers on cumulative genomic instability caused by inefficient DNA repair of dipyrimidine photoproducts. Inefficient DNA repair and subsequent translesion replication past these DNA lesions generate distinct molecular signatures of tandem CC to TT and C to T transitions at dipyrimidine sites. Since previous efforts to develop experimental strategies to enhance the repair capacity of basal keratinocytes have been limited, we have engineered the N-terminally truncated form (Δ228) UV endonuclease (UVDE) from Schizosaccharomyces pombe to include a TAT cell-penetrating peptide sequence with or without a nuclear localization signal (NLS): UVDE-TAT and UVDE-NLS-TAT...
January 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29310268/integrating-dna-structure-switch-with-branched-hairpins-for-the-detection-of-uracil-dna-glycosylase-activity-and-inhibitor-screening
#6
Jing Zhu, Qijie Hao, Yi Liu, Zhaohui Guo, Buayxigul Rustam, Wei Jiang
The detection of uracil-DNA glycosylase (UDG) activity is pivotal for its biochemical studies and the development of drugs for UDG-related diseases. Here, we explored an integrated DNA structure switch for high sensitive detection of UDG activity. The DNA structure switch containing two branched hairpins was employed to recognize UDG enzyme and generate fluorescent signal. Under the action of UDG, one branched hairpin was impelled folding into a close conformation after the excision of the single uracil. This reconfigured hairpin could immediately initiate the polymerization/nicking amplification reaction of another branched hairpin accompanying with the release of numerous G-quadruplexes (G4s)...
March 1, 2018: Talanta
https://www.readbyqxmd.com/read/29306194/downregulation-of-parp1-transcription-by-cdk4-6-inhibitors-sensitizes-human-lung-cancer-cells-to-anticancer-drug-induced-death-by-impairing-ogg1-dependent-base-excision-repair
#7
Dominika Tempka, Paulina Tokarz, Kinga Chmielewska, Magdalena Kluska, Julita Pietrzak, Żaneta Rygielska, László Virág, Agnieszka Robaszkiewicz
Hallmarks of cancer cells include uncontrolled growth and rapid proliferation; thus, cyclin-dependent kinases are a therapeutic target for cancer treatment. Treating non-small lung cancer cells with sublethal concentrations of the CDK4/6 inhibitors, ribociclib (LEE011) and palbociclib (PD0332991), which are approved by the FDA for anticancer therapies, caused cell cycle arrest in the G1 phase and suppression of poly(ADP-ribose) polymerase 1 (PARP1) transcription by inducing recruitment of the RB1-E2F1-HDAC1-EZH2 repressive complex to the PARP1 promoter...
December 29, 2017: Redox Biology
https://www.readbyqxmd.com/read/29305130/effects-of-the-ser326cys-polymorphism-in-the-dna-repair-ogg1-gene-on-cancer-cardiovascular-and-all-cause-mortality-in-the-predimed-study-modulation-by-diet
#8
Dolores Corella, Judith B Ramírez-Sabio, Oscar Coltell, Carolina Ortega-Azorín, Ramón Estruch, Miguel A Martínez-González, Jordi Salas-Salvadó, José V Sorlí, Olga Castañer, Fernando Arós, Franscisco J Garcia-Corte, Lluís Serra-Majem, Enrique Gómez-Gracia, Miquel Fiol, Xavier Pintó, Guillermo T Saez, Estefanía Toledo, Josep Basora, Montserrat Fitó, Montserrat Cofán, Emilio Ros, Jose M Ordovas
BACKGROUND: Oxidatively induced DNA damage, an important factor in cancer etiology, is repaired by oxyguanine glycosylase 1 (OGG1). The lower repair capacity genotype (homozygote Cys326Cys) in the OGG1-rs1052133 (Ser326Cys) polymorphism has been associated with cancer risk. However, no information is available in relation to cancer mortality, other causes of death, and modulation by diet. OBJECTIVE: Our aim was to evaluate the association of the OGG1-rs1052133 with total, cancer, and cardiovascular disease (CVD) mortality and to analyze its modulation by the Mediterranean diet, focusing especially on total vegetable intake as one of the main characteristics of this diet...
January 2, 2018: Journal of the Academy of Nutrition and Dietetics
https://www.readbyqxmd.com/read/29289706/an-engineered-cell-line-lacking-ogg1-and-mutyh-glycosylases-implicates-the-accumulation-of-genomic-8-oxoguanine-as-the-basis-for-paraquat-mutagenicity
#9
Preechaya Tajai, Bogdan I Fedeles, Tawit Suriyo, Panida Navasumrit, Jantamas Kanitwithayanun, John M Essigmann, Jutamaad Satayavivad
Paraquat (1,1'-dimethyl, 4,4'-bipyridinium dichloride; PQ), a widely used herbicide, is toxic to mammals through ingestion, inhalation and skin contact. Epidemiological data suggest that PQ is also mutagenic and carcinogenic, especially in high doses. The toxic and mutagenic properties of PQ are attributed to the ability of the molecule to redox-cycle, which generates reactive oxygen species (ROS) and subsequent oxidative stress. ROS also cause oxidative DNA damage such as 8-oxoguanine (8OG), a mutagenic base that, when replicated, causes G to T transversion mutations...
December 28, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29248571/the-secondary-fusarium-metabolite-aurofusarin-induces-oxidative-stress-cytotoxicity-and-genotoxicity-in-human-colon-cells
#10
Katharina Jarolim, Konstantin Wolters, Lydia Woelflingseder, Gudrun Pahlke, Julia Beisl, Hannes Puntscher, Dominik Braun, Michael Sulyok, Benedikt Warth, Doris Marko
Aurofusarin (AURO), a dimeric naphthoquinone, is produced by Fusarium fungi. Although frequently found in food and feed, toxicological studies are limited. Hence, the in vitro toxicity of AURO was investigated in the colon adenocarcinoma cell line HT29 and the non-tumorigenic colon cells HCEC-1CT. Cytotoxic effects were found at concentrations ≥1 μM by evaluating mitochondrial activity (WST-1) and cellular proliferation (sulforhodamine B assay). 10 μM of AURO induced a decrease of cells in the S-phase, measured by flow cytometry...
December 14, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/29244183/dna-damage-and-epigenetic-alteration-in-soybean-farmers-exposed-to-complex-mixture-of-pesticides
#11
Danieli Benedetti, Barbara Lopes Alderete, Claudia Telles de Souza, Johnny Ferraz Dias, Liana Niekraszewicz, Mónica Cappetta, Wilner Martínez-López, Juliana Da Silva
Exposure to pesticides can trigger genotoxic and mutagenic processes through different pathways. However, epidemiological studies are scarce, and further work is needed to find biomarkers sensitive to the health of exposed populations. Considering that there are few evaluations of soybean farmers, the aim of this study was to assess the effects of human exposure to complex mixtures of pesticides. The alkaline comet assay modified with restriction enzyme (hOGG1: human 8-oxoguanine DNA glycosylase) was used to detect oxidised guanine, and compared with the buccal micronucleus cytome assay, global methylation, haematological parameters, biochemical analyses (serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, gamma-glutamyl-transferase and butyrylcholinesterase), and particle-induced X-ray emission (PIXE) for the analysis of inorganic elements...
December 13, 2017: Mutagenesis
https://www.readbyqxmd.com/read/29244109/gadd45a-promotes-active-dna-demethylation-of-the-mmp-9-promoter-via-base-excision-repair-pathway-in-ages-treated-keratinocytes-and-in-diabetic-male-rat-skin
#12
Liyan Zhou, Wei Wang, Chuan Yang, Tingting Zeng, Mengdie Hu, Xiaoyi Wang, Na Li, Kan Sun, Chuan Wang, Jing Zhou, Meng Ren, Li Yan
Diabetes elevates matrix metalloproteinase-9 (MMP-9) levels in the skin and its keratinocytes, and activated MMP-9 impairs skin wound healing. Epigenetic regulation of the DNA methylation status within the MMP-9 promoter plays an important role in the alteration of MMP-9 expression. Our aim was to investigate the role and mechanism of growth arrest and DNA damage-inducible 45a (GADD45a), a well-known DNA demethylation regulatory protein that mediates DNA methylation, in the regulation of MMP-9 expression. In this study, we showed that GADD45a was markedly upregulated in skin tissues from patients with diabetic foot ulcers, in diabetic rats and in human keratinocyte (HaCaT) cells exposed to advanced glycation end products (AGEs)...
December 13, 2017: Endocrinology
https://www.readbyqxmd.com/read/29242626/stable-transgenerational-epigenetic-inheritance-requires-a-dna-methylation-sensing-circuit
#13
Ben P Williams, Mary Gehring
Epigenetic states are stably propagated in eukaryotes. In plants, DNA methylation patterns are faithfully inherited over many generations but it is unknown how the dynamic activities of cytosine DNA methyltransferases and 5-methylcytosine DNA glycosylases interact to maintain epigenetic homeostasis. Here we show that a methylation-sensing gene regulatory circuit centered on a 5-methylcytosine DNA glycosylase gene is required for long-term epigenetic fidelity in Arabidopsis. Disrupting this circuit causes widespread methylation losses and abnormal phenotypes that progressively worsen over generations...
December 14, 2017: Nature Communications
https://www.readbyqxmd.com/read/29240951/using-the-comet-assay-and-lysis-conditions-to-characterize-dna-lesions-from-the-acrylamide-metabolite-glycidamide
#14
Siri Helland Hansen, Agnieszka J Pawlowicz, Leif Kronberg, Kristine Bjerve Gützkow, Ann-Karin Olsen, Gunnar Brunborg
The alkaline comet assay and a cell-free system were used to characterise DNA lesions induced by treatment with glycidamide (GA), a metabolite of the food contaminant acrylamide. DNA lesions induced by GA were sensitively detected when the formamidopyrimidine-DNA-glycosylase (Fpg) enzyme was included in the comet assay. We used LC-MS to characterise modified bases from GA-treated naked DNA with and without subsequent Fpg treatment. N7-GA-Guanine and N3-GA-Adenine aglycons were detected in the supernatant showing some depurination of adducted bases; treatment of naked DNA with Fpg revealed no further increase in the adduct yield nor occurrence of other adducted nucleobases...
December 12, 2017: Mutagenesis
https://www.readbyqxmd.com/read/29237049/the-comet-assay-in-human-biomonitoring-cryopreservation-of-whole-blood-and-comparison-with-isolated-mononuclear-cells
#15
Gudrun Koppen, Sofie De Prins, An Jacobs, Vera Nelen, Greet Schoeters, Sabine A S Langie
The comet assay is often applied in human biomonitoring. Most of the time the assay is performed with isolated peripheral blood mononuclear cells (PBMC). However, using whole blood instead of isolated cells reduces processing time, and only 20 µl is sufficient for analysis. In this study, a cryopreservation protocol for human whole blood for application in the comet assay was optimised by removing excess plasma before adding freezing medium. Cryopreservation of whole blood samples (n = 30) did not increase the detected level of strand breaks and formamidopyrimidine DNA glycosylase (FPG)-sensitive sites...
December 9, 2017: Mutagenesis
https://www.readbyqxmd.com/read/29235922/dna-methylation-reprogramming-of-human-cancer-cells-by-expression-of-a-plant-5-methylcytosine-dna-glycosylase
#16
Teresa Morales-Ruiz, María Victoria García-Ortiz, Iván Devesa-Guerra, Laura Raya-Ruiz, Juan R Tejedor, Gustavo F Bayón, Marta I Sierra, Mario F Fraga, Rafael R Ariza, Teresa Roldán-Arjona
Patterns of DNA methylation, an important epigenetic modification involved in gene silencing and development, are disrupted in cancer cells. Understanding the functional significance of aberrant methylation in tumors remains challenging, due in part to the lack of suitable tools to actively modify methylation patterns. DNA demethylation caused by mammalian DNA methyltransferase inhibitors is transient and replication-dependent, whereas that induced by TET enzymes involves oxidized 5mC derivatives that perform poorly understood regulatory functions...
December 13, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/29234069/the-human-dna-glycosylases-neil1-and-neil3-excise-psoralen-induced-dna-dna-cross-links-in-a-four-stranded-dna-structure
#17
Peter R Martin, Sophie Couvé, Caroline Zutterling, Mustafa S Albelazi, Regina Groisman, Bakhyt T Matkarimov, Jason L Parsons, Rhoderick H Elder, Murat K Saparbaev
Interstrand cross-links (ICLs) are highly cytotoxic DNA lesions that block DNA replication and transcription by preventing strand separation. Previously, we demonstrated that the bacterial and human DNA glycosylases Nei and NEIL1 excise unhooked psoralen-derived ICLs in three-stranded DNA via hydrolysis of the glycosidic bond between the crosslinked base and deoxyribose sugar. Furthermore, NEIL3 from Xenopus laevis has been shown to cleave psoralen- and abasic site-induced ICLs in Xenopus egg extracts. Here we report that human NEIL3 cleaves psoralen-induced DNA-DNA cross-links in three-stranded and four-stranded DNA substrates to generate unhooked DNA fragments containing either an abasic site or a psoralen-thymine monoadduct...
December 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29233680/new-fpg-probe-chemistry-for-direct-detection-of-recombinase-polymerase-amplification-on-lateral-flow-strips
#18
Michael L Powell, Frank R Bowler, Aurore J Martinez, Catherine J Greenwood, Niall Armes, Olaf Piepenburg
Rapid, cost-effective and sensitive detection of nucleic acids has the ability to improve upon current practices employed for pathogen detection in diagnosis of infectious disease and food testing. Furthermore, if assay complexity can be reduced, nucleic acid amplification tests could be deployed in resource-limited and home use scenarios. In this study, we developed a novel Fpg (Formamidopyrimidine DNA glycosylase) probe chemistry, which allows lateral flow detection of amplification in undiluted recombinase polymerase amplification (RPA) reactions...
December 9, 2017: Analytical Biochemistry
https://www.readbyqxmd.com/read/29233176/uncoordinated-expression-of-dna-methylation-related-enzymes-in-human-cancer
#19
Jiao Liu, Xiuliang Cui, Jinhua Jiang, Dan Cao, Yufei He, Hongyang Wang
BACKGROUND: In addition to the important roles played by 5-methylcytosine (5mC), emerging evidence suggests that 5mC derivatives, such as 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC), also exhibit regulatory functions in physiological and pathological processes. Four cytosine modifications (5mC, 5hmC, 5fC and 5caC) are produced and erased by a cyclic enzymatic cascade mediated by DNA methyltransferases (DNMTs), ten-eleven translocation (TET) family enzymes and thymine DNA glycosylase (TDG)...
December 12, 2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/29227732/%C3%AE-8-oxoguanine-dna-glycosylase-overexpression-reduces-oxidative-stress-induced-mitochondrial-dysfunction-and-apoptosis-through-the-jnk-signaling-pathway-in-human-bronchial-epithelial-cells
#20
Ziying Lin, Wenya Xu, Chunyan Li, Yahong Wang, Lawei Yang, Bao'an Zou, Shenglan Gao, Weimin Yao, Zeqing Song, Gang Liu
8-Oxoguanine DNA glycosylase (OGG1) is responsible for repairing 8-oxo-7,8-dihydroguanine (8-oxoG). Our previous study demonstrated that α-OGG1 protects cells from oxidative damage-induced apoptosis and mitochondrial dysfunction in human lung cancer cells. However, the function of β-OGG1 remains to be elucidated. In this study, we demonstrated that overexpressed β-OGG1 has the same role as α-OGG1 in protecting human bronchial epithelial cells from apoptosis and mitochondrial dysfunction. Furthermore, flow cytometry, confocal microscopy, and western blotting showed that the overexpression of β-OGG1 could block oxidant-induced apoptosis in human bronchial epithelial cells...
December 2017: DNA and Cell Biology
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