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DNA glycosylases

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https://www.readbyqxmd.com/read/27918552/hmyh-and-hmth1-cooperate-for-survival-in-mismatch-repair-defective-t-cell-acute-lymphoblastic-leukemia
#1
S Eshtad, Z Mavajian, S G Rudd, T Visnes, J Boström, M Altun, T Helleday
hMTH1 is an 8-oxodGTPase that prevents mis-incorporation of free oxidized nucleotides into genomic DNA. Base excision and mismatch repair pathways also restrict the accumulation of oxidized lesions in DNA by removing the mis-inserted 8-oxo-7,8-dihydro-2'-deoxyguanosines (8-oxodGs). In this study, we aimed to investigate the interplay between hMYH DNA glycosylase and hMTH1 for cancer cell survival by using mismatch repair defective T-cell acute lymphoblastic leukemia (T-ALL) cells. To this end, MYH and MTH1 were silenced individually or simultaneously using small hairpin RNAs...
December 5, 2016: Oncogenesis
https://www.readbyqxmd.com/read/27914857/imidacloprid-induces-various-toxicological-effects-related-to-the-expression-of-3%C3%AE-hsd-nr5a1-and-ogg1-genes-in-mature-and-immature-rats
#2
Amany Abdel-Rahman Mohamed, Wafaa A M Mohamed, Safaa I Khater
This study aimed to evaluate the adverse effects of the insecticide imidacloprid (IMI) on male spermatogenesis, steroidogenesis, and DNA damage in sexually mature and immature rats. Forty male rats (mature and immature) were equally divided into four groups: two mature and two immature groups. IMI groups of both ages were orally administered IMI in corn oil at a concentration of 1 mg/mL for kg BW/day, whereas their respective controls were orally administered corn oil only (1 mL/kg of body weight) daily for 65 days...
November 30, 2016: Environmental Pollution
https://www.readbyqxmd.com/read/27908238/thermodynamic-analysis-of-fast-stages-of-specific-lesion-recognition-by-dna-repair-enzymes
#3
REVIEW
N A Kuznetsov, O S Fedorova
The methodology of determination of the thermodynamic parameters of fast stages of recognition and cleavage of DNA substrates is described for the enzymatic processes catalyzed by DNA glycosylases Fpg and hOGG1 and AP endonuclease APE1 during base excision repair (BER) pathway. For this purpose, stopped-flow pre-steady-state kinetic analysis of tryptophan fluorescence intensity changes in proteins and fluorophores in DNA substrates was performed at various temperatures. This approach made it possible to determine the changes of standard Gibbs free energy, enthalpy, and entropy of sequential steps of DNA-substrate binding, as well as activation enthalpy and entropy for the transition complex formation of the catalytic stage...
October 2016: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/27903453/repair-of-8-oxo-7-8-dihydroguanine-in-prokaryotic-and-eukaryotic-cells-properties-and-biological-roles-of-the-fpg-and-ogg1-dna-n-glycosylases
#4
Serge Boiteux, Franck Coste, Bertrand Castaing
Oxidatively damaged DNA results from the attack of sugar and base moieties by reactive oxygen species (ROS), which are formed as byproducts of normal cell metabolism and during exposure to endogenous or exogenous chemical or physical agents. Guanine, having the lowest redox potential, is the DNA base the most susceptible to oxidation, yielding products such as 8-oxo-7,8-dihydroguanine (8-oxoG) and 2-6-diamino-4-hydroxy-5-formamidopyrimidine (FapyG). In DNA, 8-oxoG was shown to be mutagenic yielding GC to TA transversions upon incorporation of dAMP opposite this lesion by replicative DNA polymerases...
November 26, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27890638/aberrant-base-excision-repair-pathway-of-oxidatively-damaged-dna-implications-for-degenerative-diseases
#5
Ibtissam Talhaoui, Bakhyt T Matkarimov, Thierry Tchenio, Dmitry O Zharkov, Murat K Saparbaev
In cellular organisms composition of DNA is constrained to only four nucleobases A, G, T and C, except for minor DNA base modifications such as methylation which serves for defence against foreign DNA or gene expression regulation. Interestingly, this severe evolutionary constraint among other things demands DNA repair systems to discriminate between regular and modified bases. DNA glycosylases specifically recognize and excise damaged bases among vast majority of regular bases in the base excision repair (BER) pathway...
November 24, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27880870/formation-and-processing-of-dna-damage-substrates-for-the-hneil-enzymes
#6
Aaron M Fleming, Cynthia J Burrows
Reactive oxygen species (ROS) are harnessed by the cell for signaling at the same time as being detrimental to cellular components such as DNA. The genome and transcriptome contain instructions that can alter cellular processes when oxidized. The guanine (G) heterocycle in the nucleotide pool, DNA, or RNA is the base most prone to oxidation. The oxidatively-derived products of G consistently observed in high yields from hydroxyl radical, carbonate radical, or singlet oxygen oxidations under conditions modeling the cellular reducing environment are discussed...
November 20, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27875297/glycogen-synthase-kinase-3-gsk-3-mediated-phosphorylation-of-uracil-n-glycosylase-2-ung2-facilitates-repair-of-floxuridine-induced-dna-lesions-and-promotes-cell-survival
#7
Carly A Baehr, Catherine J Huntoon, Song-My Hoang, Calvin R Jerde, Larry M Karnitz
Uracil N-glycosylase 2 (UNG2), the nuclear isoform of UNG, catalyzes the removal of uracil or 5-fluorouracil lesions that accumulate in DNA following treatment with the anti-cancer agents 5-fluorouracil and 5-fluorodeoxyuridine (floxuridine), a 5-fluorouracil metabolite. By repairing these DNA lesions before they can cause cell death, UNG2 promotes cancer cell survival and is therefore critically involved in tumor resistance to these agents. However, the mechanisms by which UNG2 is regulated remain unclear...
November 14, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27871818/oxidatively-generated-base-modifications-in-dna-not-only-carcinogenic-risk-factor-but-also-regulatory-mark
#8
Marco Seifermann, Bernd Epe
The generation of DNA modifications in cells is in most cases accidental and associated with detrimental consequences such as increased mutation rates and an elevated risk of malignant transformation. Accordingly, repair enzymes involved in the removal of the modifications have primarily a protective function. Among the well-established exceptions of this rule are 5-methylcytosine and uracil, which are generated in DNA enzymatically under controlled conditions and fulfill important regulatory functions in DNA as epigenetic marks and in antibody diversification, respectively...
November 18, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27865982/hide-and-seek-how-do-dna-glycosylases-locate-oxidatively-damaged-dna-bases-amidst-a-sea-of-undamaged-bases
#9
Andrea J Lee, Susan S Wallace
The first step of the base excision repair (BER) pathway responsible for removing oxidative DNA damage utilizes DNA glycosylases to find and remove the damaged DNA base. How glycosylases find the damaged base amidst a sea of undamaged bases has long been a question in the BER field. Single molecule total internal reflection fluorescence microscopy (SM TIRFM) experiments have allowed for an exciting look into this search mechanism and have found that DNA glycosylases scan along the DNA backbone in a bidirectional and random fashion...
November 16, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27864332/weak-silica-nanomaterial-induced-genotoxicity-can-be-explained-by-indirect-dna-damage-as-shown-by-the-ogg1-modified-comet-assay-and-genomic-analysis
#10
Stefan Pfuhler, Thomas R Downs, Ashley J Allemang, Yuching Shan, Meredith E Crosby
In a previous study, 15-nm silica nanoparticles (NPs) caused small increases in DNA damage in liver as measured in the in vivo comet and micronucleus assays after intravenous administration to rats at their maximum tolerated dose, a worst-case exposure scenario. Histopathological examination supported a particle-induced, tissue damage-mediated inflammatory response. This study used a targeted approach to provide insight into the mode of action (MoA) by examining transcriptional regulation of genes in liver in a time and dose-dependent manner at 1, 2, 4, 8 and 24 h after intravenous administration of 15-nm silica NPs...
November 17, 2016: Mutagenesis
https://www.readbyqxmd.com/read/27859411/dna-demethylation-pathways-additional-players-and-regulators
#11
Matthias Bochtler, Agnieszka Kolano, Guo-Liang Xu
DNA demethylation can occur passively by "dilution" of methylation marks by DNA replication, or actively and independently of DNA replication. Direct conversion of 5-methylcytosine (5mC) to cytosine (C), as originally proposed, does not occur. Instead, active DNA methylation involves oxidation of the methylated base by ten-eleven translocations (TETs), or deamination of the methylated or a nearby base by activation induced deaminase (AID). The modified nucleotide, possibly together with surrounding nucleotides, is then replaced by the BER pathway...
November 16, 2016: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/27854545/mir-29b-targets-lpl-and-tdg-genes-and-regulates-apoptosis-and-triglyceride-production-in-mecs
#12
Yuwei Yang, Qiqi Pan, Boxing Sun, Runjun Yang, Xibi Fang, Xin Liu, Xianzhong Yu, Zhihui Zhao
microRNAs are involved in various biological processes by regulating the degradation or repressing the translation of target genes. In this study, the target genes of miR-29b were analyzed and predicted by bioinformatics. And lipoprotein lipase (LPL) and thymine DNA glycosylase (TDG) were selected for further validation by dual luciferase reporter assay. In addition, we investigated the effects of miR-29b on triglyceride synthesis and mammary epithelial cell (MEC) apoptosis. The result showed that luciferase activity was significantly lower in cells that miR-29b cotransfected with LPL and TDG gene reporter vectors (pmiR-RB-REPORT-LPL-WT, pmiR-RB-REPORT-TDG-WT) than in cells of miR-29b cotransfected with gene reporter vectors (pmiR-RB-REPORT-LPL-mut and pmiR-RB-REPORT-LPL-si; pmiR-RB-REPORT-TDG-mut and pmiR-RB-REPORT-TDG-si) (p < 0...
December 2016: DNA and Cell Biology
https://www.readbyqxmd.com/read/27836975/a-conserved-tripeptide-sequence-at-the-c-terminus-of-the-poxvirus-dna-processivity-factor-d4-is-essential-for-protein-integrity-and-function
#13
Manunya Nuth, Hancheng Guan, Robert P Ricciardi
Vaccinia virus (VACV) is a poxvirus member, and the VACV D4 protein serves both as a uracil-DNA glycosylase (UDG) and as an essential component required for processive DNA synthesis. The VACV A20 protein has no known catalytic function itself, but associates with D4 to form the D4-A20 heterodimer that functions as the poxvirus DNA processivity factor. The heterodimer enables the DNA polymerase to efficiently synthesize extended strands of DNA. Upon characterizing the interaction between D4 and A20, we observed that the C-terminus of D4 is susceptible to perturbation...
November 11, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27836324/the-major-arabidopsis-thaliana-apurinic-apyrimidinic-endonuclease-arp-is-involved-in-the-plant-nucleotide-incision-repair-pathway
#14
Zhiger Akishev, Sabira Taipakova, Botagoz Joldybayeva, Caroline Zutterling, Izat Smekenov, Alexander A Ishchenko, Dmitry O Zharkov, Amangeldy K Bissenbaev, Murat Saparbaev
Apurinic/apyrimidinic (AP) endonucleases are important DNA repair enzymes involved in two overlapping pathways: DNA glycosylase-initiated base excision (BER) and AP endonuclease-initiated nucleotide incision repair (NIR). In the BER pathway, AP endonucleases cleave DNA at AP sites and 3'-blocking moieties generated by DNA glycosylases, whereas in NIR, the same AP endonucleases incise DNA 5' to a wide variety of oxidized bases. The flowering plant Arabidopsis thaliana contains three genes encoding homologues of major human AP endonuclease 1 (APE1): Arp, Ape1L and Ape2...
October 29, 2016: DNA Repair
https://www.readbyqxmd.com/read/27833032/mth1-as-a-nucleotide-pool-sanitizing-enzyme-friend-or-foe
#15
Yusaku Nakabeppu, Eiko Ohta, Nona Abolhassani
8-Oxo-7,8-dihydroguanine (GO) can originate as 8-oxo-7,8-dihydro-2'-deoxyguanosine 5'-triphosphate (8-oxo-dGTP), an oxidized form of dGTP in the nucleotide pool, or by direct oxidation of guanine base in DNA. Accumulation of GO in cellular genomes can result in mutagenesis or programmed cell death, and is thus minimized by the actions of MutT homolog-1 (MTH1) with 8-oxo-dGTPase, OGG1 with GO DNA glycosylase and MutY homolog (MUTYH) with adenine DNA glycosylase. Studies on Mth1/Ogg1/Mutyh-triple knockout mice demonstrated that the defense systems efficiently minimize GO accumulation in cellular genomes, and thus maintain low incidences of spontaneous mutagenesis and tumorigenesis...
November 7, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27825529/toehold-mediated-strand-displacement-reaction-dependent-fluorescent-strategy-for-sensitive-detection-of-uracil-dna-glycosylase-activity
#16
Yushu Wu, Lei Wang, Wei Jiang
Sensitive detection of uracil-DNA glycosylase (UDG) activity is beneficial for evaluating the repairing process of DNA lesions. Here, toehold-mediated strand displacement reaction (TSDR)-dependent fluorescent strategy was constructed for sensitive detection of UDG activity. A single-stranded DNA (ssDNA) probe with two uracil bases and a trigger sequence were designed. A hairpin probe with toehold domain was designed, and a reporter probe was also designed. Under the action of UDG, two uracil bases were removed from ssDNA probe, generating apurinic/apyrimidinic (AP) sites...
October 21, 2016: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/27818579/visualizing-the-search-for-radiation-damaged-dna-bases-in-real-time
#17
Andrea J Lee, Susan S Wallace
The Base Excision Repair (BER) pathway removes the vast majority of damages produced by ionizing radiation, including the plethora of radiation-damaged purines and pyrimidines. The first enzymes in the BER pathway are DNA glycosylases, which are responsible for finding and removing the damaged base. Although much is known about the biochemistry of DNA glycosylases, how these enzymes locate their specific damage substrates among an excess of undamaged bases has long remained a mystery. Here we describe the use of single molecule fluorescence to observe the bacterial DNA glycosylases, Nth, Fpg and Nei, scanning along undamaged and damaged DNA...
November 2016: Radiation Physics and Chemistry
https://www.readbyqxmd.com/read/27818081/enhanced-sensitivity-of-neil1-mice-to-chronic-uvb-exposure
#18
Marcus J Calkins, Vladimir Vartanian, Nichole Owen, Guldal Kirkali, Pawel Jaruga, Miral Dizdaroglu, Amanda K McCullough, R Stephen Lloyd
Oxidative stress and reactive oxygen species (ROS)-induced DNA base damage are thought to be central mediators of UV-induced carcinogenesis and skin aging. However, increased steady-state levels of ROS-induced DNA base damage have not been reported after chronic UV exposure. Accumulation of ROS-induced DNA base damage is governed by rates of lesion formation and repair. Repair is generally performed by Base Excision Repair (BER), which is initiated by DNA glycosylases, such as 8-oxoguanine glycosylase and Nei-Endonuclease VIII-Like 1 (NEIL1)...
October 28, 2016: DNA Repair
https://www.readbyqxmd.com/read/27816939/o-glcnacylation-of-ogg1-impairs-oxidative-mitochondrial-dna-lesion-repair-in-diabetic-hearts
#19
Federico Cividini, Brian T Scott, Anzhi Dai, Wenlong Han, Jorge Suarez, Julieta Diaz-Juarez, Tanja Diemer, Darren E Casteel, Wolfgang H Dillmann
Mitochondrial DNA (mtDNA) damage in cardiac myocytes resulting from increased oxidative stress is emerging as an important factor in the pathogenesis of diabetic cardiomyopathy. A prevalent lesion that occurs in mtDNA damage is the formation of 8-hydroxy-2-deoxyguanosine (8-OHdG), which can cause mutations if not repaired properly by 8-oxoguanine DNA glycosylase (Ogg1). Although the mtDNA repair machinery has been described in cardiac myocytes, the regulation of this repair has been incompletely investigated...
November 5, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27815903/analysis-of-nuclear-uracil-dna-glycosylase-nudg-turnover-during-the-cell-cycle
#20
Jennifer A Fischer, Salvatore J Caradonna
Uracil-DNA glycosylases (UDG/UNG) are enzymes that remove uracil from DNA and initiate base-excision repair. These enzymes play a key role in maintaining genomic integrity by reducing the mutagenic events caused by G:C to A:T transition mutations. The recent finding that a family of RNA editing enzymes (AID/APOBECs) can deaminate cytosine in DNA has raised the interest in these base-excision repair enzymes. The methodology presented here focuses on determining the regulation of the nuclear isoform of uracil-DNA glycosylase (nUDG), a 36,000 Da protein...
2017: Methods in Molecular Biology
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