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https://www.readbyqxmd.com/read/28218666/the-ageing-brain-effects-on-dna-repair-and-dna-methylation-in-mice
#1
Sabine A S Langie, Kerry M Cameron, Gabriella Ficz, David Oxley, Bartłomiej Tomaszewski, Joanna P Gorniak, Lou M Maas, Roger W L Godschalk, Frederik J van Schooten, Wolf Reik, Thomas von Zglinicki, John C Mathers
Base excision repair (BER) may become less effective with ageing resulting in accumulation of DNA lesions, genome instability and altered gene expression that contribute to age-related degenerative diseases. The brain is particularly vulnerable to the accumulation of DNA lesions; hence, proper functioning of DNA repair mechanisms is important for neuronal survival. Although the mechanism of age-related decline in DNA repair capacity is unknown, growing evidence suggests that epigenetic events (e.g., DNA methylation) contribute to the ageing process and may be functionally important through the regulation of the expression of DNA repair genes...
February 17, 2017: Genes
https://www.readbyqxmd.com/read/28202616/dna-repair-interacts-with-autophagy-to-regulate-inflammatory-responses-to-pulmonary-hyperoxia
#2
Yan Ye, Ping Lin, Weidong Zhang, Shirui Tan, Xikun Zhou, Rongpeng Li, Qinqin Pu, Jonathan L Koff, Archana Dhasarathy, Feng Ma, Xin Deng, Jianxin Jiang, Min Wu
Oxygen is supplied as a supportive treatment for patients suffering from acute respiratory distress syndrome. Unfortunately, high oxygen concentration increases reactive oxygen species generation, which causes DNA damage and ultimately cell death in the lung. Although 8-oxoguanine-DNA glycosylase (OGG-1) is involved in repairing hyperoxia-mediated DNA damage, the underlying molecular mechanism remains elusive. In this study, we report that ogg-1-deficient mice exhibited a significant increase of proinflammatory cytokines (TNF-α, IL-6, and IFN-γ) in the lung after being exposed to 95% oxygen...
February 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28159922/base-excision-repair-imbalance-in-colorectal-cancer-has-prognostic-value-and-modulates-response-to-chemotherapy
#3
Natalia M Leguisamo, Helena C Gloria, Antonio N Kalil, Talita V Martins, Daniel B Azambuja, Lisiane B Meira, Jenifer Saffi
Colorectal cancer (CRC) is prevalent worldwide, and treatment often involves surgery and genotoxic chemotherapy. DNA repair mechanisms, such as base excision repair (BER) and mismatch repair (MMR), may not only influence tumour characteristics and prognosis but also dictate chemotherapy response. Defective MMR contributes to chemoresistance in colorectal cancer. Moreover, BER affects cellular survival by repairing genotoxic base damage in a process that itself can disrupt metabolism. In this study, we characterized BER and MMR gene expression in colorectal tumours and the association between this repair profile with patients' clinical and pathological features...
January 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28150947/sequencing-the-mouse-genome-for-the-oxidatively-modified-base-8-oxo-7-8-dihydroguanine-by-og-seq
#4
Yun Ding, Aaron M Fleming, Cynthia J Burrows
Oxidatively derived damage to the genome can yield the base 8-oxo-7,8-dihydroguanine (OG). In vitro studies hypothesized OG would preferentially form in 5`-GG-3` sequence contexts when the genome is exposed to reactive oxygen species. Herein, OG locations in the genome were studied by development and implementation of "OG-Seq" to sequence OG sites via next-generation sequencing at ~0.15-kb resolution. The results of this study found ~10,000 regions of OG enrichment in WT mouse embryonic fibroblasts (MEFs) and ~18,000 regions when the OG repair glycosylase Ogg1 was knocked out...
February 2, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28147323/the-dna-repair-function-of-cux1-contributes-to-radioresistance
#5
Zubaidah M Ramdzan, Vasudeva Ginjala, Jordan B Pinder, Dudley Chung, Caroline M Donovan, Simran Kaur, Lam Leduy, Graham Dellaire, Shridar Ganesan, Alain Nepveu
Ionizing radiation generates a broad spectrum of oxidative DNA lesions, including oxidized base products, abasic sites, single-strand breaks and double-strand breaks. The CUX1 protein was recently shown to function as an auxiliary factor that stimulates enzymatic activities of OGG1 through its CUT domains. In the present study, we investigated the requirement for CUX1 and OGG1 in the resistance to radiation. Cancer cell survival following ionizing radiation is reduced by CUX1 knockdown and increased by higher CUX1 expression...
January 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28143930/oxidative-dna-damage-is-epigenetic-by-regulating-gene-transcription-via-base-excision-repair
#6
Aaron M Fleming, Yun Ding, Cynthia J Burrows
Reactive oxygen species (ROS) have emerged as important cellular-signaling agents for cellular survival. Herein, we demonstrate that ROS-mediated oxidation of DNA to yield 8-oxo-7,8-dihydroguanine (OG) in gene promoters is a signaling agent for gene activation. Enhanced gene expression occurs when OG is formed in guanine-rich, potential G-quadruplex-forming sequences (PQS) in promoter-coding strands, initiating base excision repair (BER) by 8-oxoguanine DNA glycosylase (OGG1), yielding an abasic site (AP). The AP enables melting of the duplex to unmask the PQS, adopting a G-quadruplex fold in which apurinic/apyrimidinic endonuclease 1 (APE1) binds, but inefficiently cleaves, the AP for activation of vascular endothelial growth factor (VEGF) or endonuclease III-like protein 1 (NTHL1) genes...
January 31, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28129013/oxidative-dna-damage-and-reduced-expression-of-dna-repair-genes-role-in-primary-open-angle-glaucoma-poag
#7
Kuldeep Mohanty, Rima Dada, Tanuj Dada
BACKGROUND: Controversy exists regarding the role of oxidative DNA damage and DNA repair in primary open angle glaucoma (POAG). We performed a case control study to test the hypothesis that oxidative DNA damage and base excision repair (BER) genes PARP1 and OGG1 are involved in POAG pathogenesis. MATERIALS AND METHODS: The study included 116 POAG patients and 116 cataract patients as controls. The 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels were measured by ELISA...
January 27, 2017: Ophthalmic Genetics
https://www.readbyqxmd.com/read/28125528/mitochondrial-dna-damage-initiates-acute-lung-injury-and-multi-organ-system-failure-evoked-in-rats-by-intra-tracheal-pseudomonas-aeruginosa
#8
Yann-Leei Lee, Boniface Obiako, Olena M Gorodnya, Mykhaylo V Ruchko, Jamie L Kuck, Viktor M Pastukh, Glenn L Wilson, Jon D Simmons, Mark N Gillespie
Although studies in rat cultured pulmonary artery endothelial cells, perfused lungs, and intact mice support the concept that oxidative mitochondrial (mt) DNA damage triggers acute lung injury (ALI), it has not yet been determined whether enhanced mtDNA repair forestalls development of ALI and its progression to multiple organ system failure (MOSF). Accordingly, here we examined the effect of a fusion protein construct targeting the DNA glycosylase, Ogg1, to mitochondria in a rat model intra-tracheal P. aeruginosa (strain 103; PA103)-induced ALI and MOSF...
January 25, 2017: Shock
https://www.readbyqxmd.com/read/28098999/dna-deformation-coupled-recognition-of-8-oxoguanine-conformational-kinetic-gating-in-human-dna-glycosylase
#9
Haoquan Li, Anton V Endutkin, Christina Bergonzo, Lin Fu, Arthur 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 (O(8) and H(7)). 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...
February 22, 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-and-medicine
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
REVIEW
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
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