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https://www.readbyqxmd.com/read/28098999/dna-deformation-coupled-recognition-of-8-oxoguanine-conformational-kinetic-gating-in-human-dna-glycosylase
#1
Haoquan Li, Anton V Endutkin, Christina Bergonzo, Fu Lin, Arthur P Grollman, Dmitry O Zharkov, Carlos Simmerling
8-Oxoguanine (8-oxoG), a mutagenic DNA lesion generated under oxidative stress, differs from its precursor guanine by only two substitutions (O8 and H7). Human 8-oxoguanine glycosylase 1 (OGG1) can locate and remove 8-oxoG through extrusion and excision. To date, it remains unclear how OGG1 efficiently distinguishes 8-oxoG from a large excess of undamaged DNA bases. We recently showed that formamidopyrimidine-DNA glycosylase (Fpg), a bacterial functional analog of OGG1, can selectively facilitate eversion of oxoG by stabilizing several intermediate states, and it is intriguing whether OGG1 also employs a similar mechanism in lesion recognition...
January 18, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28087410/repair-of-8-oxog-a-mismatches-by-the-mutyh-glycosylase-mechanism-metals-medicine
#2
REVIEW
Douglas M Banda, Nicole N Nuñez, Michael A Burnside, Katie M Bradshaw, Sheila S David
Reactive oxygen and nitrogen species (RONS) may infringe on the passing of pristine genetic information by inducing DNA inter- and intra-strand crosslinks, protein-DNA crosslinks, and chemical alterations to the sugar or base moieties of DNA. 8-Oxo-7,8-dihydroguanine (8-oxoG) is one of the most prevalent DNA lesions formed by RONS and is repaired through the base excision repair (BER) pathway involving the DNA repair glycosylases OGG1 and MUTYH in eukaryotes. MUTYH removes adenine (A) from 8-oxoG:A mispairs, thus mitigating the potential of G:C to T:A transversion mutations from occurring in the genome...
January 10, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28079919/copper-oxide-nanoparticles-and-copper-sulphate-act-as-antigenotoxic-agents-in-drosophila-melanogaster
#3
Mohamed Alaraby, Alba Hernández, Ricard Marcos
The biological reactivity of metal and metal oxide nanomaterials is attributed to their redox properties, which would explain their pro- or anti-cancer properties depending on exposure circumstances. In this sense, copper oxide nanoparticles (CuONP) have been proposed as a potential anti-tumoral agent. The aim of this study was to assess if CuONP can exert antigenotoxic effects using Drosophila melanogaster as an in vivo model. Genotoxicity was induced by two well-known genotoxic compounds, namely potassium dichromate (PD) and ethyl methanesulfonate (EMS)...
January 12, 2017: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/28052067/the-paradoxical-effects-of-different-hepatitis-c-viral-loads-on-host-dna-damage-and-repair-abilities
#4
Shu-Chi Wang, Kuan-Ru Lai, Chia-Yang Li, Chi-Shiun Chiang, Guann-Yi Yu, Naoya Sakamoto, Wen-Yu Tu, Meng-Hsuan Hsieh, Jee-Fu Huang, Wan-Long Chuang, Chia-Yen Dai, Ming-Lung Yu
Hepatitis C virus (HCV)-induced hepatic stress is associated with increased oxidative DNA damage and has been implicated in hepatic inflammation. However, HCV infection and replication are uneven and vary among individual hepatocytes. To investigate the effect of the viral load on host DNA damage, we used an Enhanced Yellow Fluorescent Protein gene (EYFP)-tagged HCV virus to distinguish between HCV intracellular high viral load (HVL) cells and low viral load (LVL) cells. The cell sorting efficiency was confirmed by the high expression of the HCV polyprotein...
2017: PloS One
https://www.readbyqxmd.com/read/28034960/elevated-dna-oxidation-and-dna-repair-enzyme-expression-in-brain-white-matter-in-major-depressive-disorder
#5
Attila Szebeni, Katalin Szebeni, Timothy P DiPeri, Luke A Johnson, Craig A Stockmeier, Jessica D Crawford, Michelle J Chandley, Liza J Hernandez, Katherine C Burgess, Russell W Brown, Gregory A Ordway
BACKGROUND: Pathology of white matter in brains of patients with major depressive disorder (MDD) is well-documented, but the cellular and molecular basis of this pathology are poorly understood. METHODS: Levels of DNA oxidation and gene expression of DNA damage repair enzymes were measured in Brodmann area 10 (BA10) and/or amygdala (uncinate fasciculus) white matter tissue from brains of MDD (n=10) and psychiatrically normal control donors (n=13). DNA oxidation was also measured in BA10 white matter of schizophrenia donors (n=10) and in prefrontal cortical white matter from control rats (n=8) and rats with repeated stress-induced anhedonia (n=8)...
December 29, 2016: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28010926/increased-methylation-of-repetitive-elements-and-dna-repair-genes-is-associated-with-higher-dna-oxidation-in-children-in-an-urbanized-industrial-environment
#6
Isabel Alvarado-Cruz, Marco Sánchez-Guerra, Leticia Hernández-Cadena, Andrea De Vizcaya-Ruiz, Violeta Mugica, Nadia Azenet Pelallo-Martínez, María de Jesús Solís-Heredia, Hyang-Min Byun, Andrea Baccarelli, Betzabet Quintanilla-Vega
DNA methylation in DNA repair genes participates in the DNA damage regulation. Particulate matter (PM), which has metals and polycyclic aromatic hydrocarbons (PAHs) adsorbed, among others has been linked to adverse health outcomes and may modify DNA methylation. To evaluate PM exposure impact on repetitive elements and gene-specific DNA methylation and DNA damage, we conducted a cross-sectional study in 150 schoolchildren (7-10 years old) from an urbanized, industrial area of the metropolitan area of Mexico City (MAMC), which frequently exhibits PM concentrations above safety standards...
January 2017: Mutation Research
https://www.readbyqxmd.com/read/27995963/histone-deacetylase-inhibitors-mediate-dna-damage-repair-in-ameliorating-hemorrhagic-cystitis
#7
Subhash Haldar, Christopher Dru, Rajeev Mishra, Manisha Tripathi, Frank Duong, Bryan Angara, Ana Fernandez, Moshe Arditi, Neil A Bhowmick
Hemorrhagic cystitis is an inflammatory and ulcerative bladder condition associated with systemic chemotherapeutics, like cyclophosphomide. Earlier, we reported reactive oxygen species resulting from cyclophosphamide metabolite, acrolein, causes global methylation followed by silencing of DNA damage repair genes. Ogg1 (8-oxoguanine DNA glycosylase) is one such silenced base excision repair enzyme that can restore DNA integrity. The accumulation of DNA damage results in subsequent inflammation associated with pyroptotic death of bladder smooth muscle cells...
December 20, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27993944/effects-of-airborne-toxicants-on-pulmonary-function-and-mitochondrial-dna-damage-in-rodent-lungs
#8
William L Rumsey, Brian Bolognese, Alicia B Davis, Pearl L Flamberg, Joseph P Foley, Steven R Katchur, Charles J Kotzer, Ruth R Osborn, Patricia L Podolin
Inhalation of airborne toxicants such as cigarette smoke and ozone is a shared health risk among the world's populations. The use of toxic herbicides like paraquat (PQ) is restricted by many countries, yet in the developing world PQ has demonstrable ill effects. The present study examined changes in pulmonary function, mitochondrial DNA (mtDNA) integrity and markers of DNA repair induced by acute or repeated exposure of PQ to rats. Similar to cigarette smoke and ozone, PQ promotes oxidative stress, and the impact of PQ on mtDNA was compared with that obtained with these agents...
December 18, 2016: Mutagenesis
https://www.readbyqxmd.com/read/27939754/increasing-no-level-regulates-apoptosis-and-inflammation-in-macrophages-after-2-chloroethyl-ethyl-sulphide-challenge
#9
Satish Sagar, Soumya Ranjan Parida, Silpa Sabnam, Huma Rizwan, Sweta Pal, Mitali Madhusmita Swain, Arttatrana Pal
Generation of nitric oxide (NO) in cellular compartments acts in a redox-dependent manner to counteract oxidative stress either by directly acting as an antioxidant through scavenging superoxide anions (O2(-)), to form peroxynitrite (ONOO-) or acting as a signaling molecule, altering gene expression that triggers various physiological processes. However, the molecular mechanisms of macrophage activation and NO production leads to apoptosis and inflammation after 2-chloroethyl ethyl sulphide (CEES) exposure remains unclear...
December 9, 2016: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/27932951/high-pressure-induced-mtdna-alterations-in-retinal-ganglion-cells-and-subsequent-apoptosis
#10
Sheng-Hai Zhang, Feng-Juan Gao, Zhong-Mou Sun, Ping Xu, Jun-Yi Chen, Xing-Huai Sun, Ji-Hong Wu
Purpose: Our previous study indicated that mitochondrial DNA (mtDNA) damage and mutations are crucial to the progressive loss of retinal ganglion cells (RGCs) in a glaucomatous rat model. In this study, we examined whether high pressure could directly cause mtDNA alterations and whether the latter could lead to mitochondrial dysfunction and RGC death. Methods: Primary cultured rat RGCs were exposed to 30 mm Hg of hydrostatic pressure (HP) for 12, 24, 48, 72, 96 and 120 h. mtDNA alterations and mtDNA repair/replication enzymes OGG1, MYH and polymerase gamma (POLG) expressions were also analyzed...
2016: Frontiers in Cellular Neuroscience
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
#11
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...
February 2017: Environmental Pollution
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
#12
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 27, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27894683/biomonitoring-of-humans-exposed-to-arsenic-chromium-nickel-vanadium-and-complex-mixtures-of-metals-by-using-the-micronucleus-test-in-lymphocytes
#13
REVIEW
Balasubramanyam Annangi, Stefano Bonassi, Ricard Marcos, Alba Hernández
Various metals have demonstrated genotoxic and carcinogenic potential via different mechanisms. Until now, biomonitoring and epidemiological studies have been carried out to assess the genotoxic risk to exposed human populations. In this sense, the use of the micronucleus assay in peripheral blood lymphocytes has proven to be a useful tool to determine increased levels of DNA damage, as a surrogate biomarker of cancer risk. Here we review those biomonitoring studies focused on people exposed to arsenic, chromium, nickel, vanadium and complex mixtures of metals...
October 2016: Mutation Research
https://www.readbyqxmd.com/read/27871818/oxidatively-generated-base-modifications-in-dna-not-only-carcinogenic-risk-factor-but-also-regulatory-mark
#14
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/27870262/the-role-of-base-excision-repair-in-pathogenesis-of-breast-cancer-in-the-polish-population
#15
Magda Cuchra, Bartosz Mucha, Lukasz Markiewicz, Karolina Przybylowska-Sygut, Dariusz Pytel, Arkadiusz Jeziorski, Radzisław Kordek, Ireneusz Majsterek
Breast cancer (BC) is leading type of cancer among group of women, which determines almost 23% of invasive cancers. It has been reported repeatedly that the level of oxidative stress is higher for BC in comparison to cancer-free woman. The goal of the present study was to evaluate the role of base excision repair (BER) pathway in the development of BC. One-hundred seventy-one women with confirmed BC and 222 healthy controls were enrolled in presented study. The level of oxidative DNA damage and the kinetic of their repair were analyzed by the modified alkaline comet assay...
December 2016: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/27865706/age-related-length-variability-of-polymorphic-cag-repeats
#16
Monica Sanchez-Contreras, Fernando Cardozo-Pelaez
Somatic instability of CAG repeats has been associated with the clinical progression of CAG repeat diseases. Aging and DNA repair processes influence the somatic stability of CAG repeat in disease and in mouse models. However, most of the studies have focused on genetically engineered transgenic repeats and little is known about the stability of naturally polymorphic CAG repeats. To study whether age and/or DNA repair activity have an effect on the somatic stability of CAG repeats, we analyzed variations of the length of naturally polymorphic CAG repeats in the striatum of young and aged WT and ogg1 KO mice...
January 2017: DNA Repair
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
#17
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...
January 2017: Mutagenesis
https://www.readbyqxmd.com/read/27850995/1359-ogg1-and-tfam-modifications-of-mitochondrial-dna-damage-in-septic-cardiac-dysfunction
#18
Jun-Ichi Hirata, Munehiko Ohya
No abstract text is available yet for this article.
December 2016: Critical Care Medicine
https://www.readbyqxmd.com/read/27833032/mth1-as-a-nucleotide-pool-sanitizing-enzyme-friend-or-foe
#19
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/27816939/o-glcnacylation-of-8-oxoguanine-dna-glycosylase-ogg1-impairs-oxidative-mitochondrial-dna-lesion-repair-in-diabetic-hearts
#20
Federico Cividini, Brian T Scott, Anzhi Dai, Wenlong Han, Jorge Suarez, Julieta Diaz-Juarez, Tanja Diemer, Darren E Casteel, Wolfgang H Dillmann
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 when 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. Here we report that the hearts of type 1 diabetic mice, despite having increased Ogg1 protein levels, had significantly lower Ogg1 activity than the hearts of control, non-type 1 diabetic mice...
December 16, 2016: Journal of Biological Chemistry
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