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https://www.readbyqxmd.com/read/27909884/differential-role-of-wnt-signaling-and-base-excision-repair-pathways-in-gastric-adenocarcinoma-aggressiveness
#1
Alireza Korourian, Raheleh Roudi, Ahmad Shariftabrizi, Elham Kalantari, Kambiz Sotoodeh, Zahra Madjd
Aberrant activation of Wnt and base excision repair (BER) signaling pathways are implicated in tumor progression and chemotherapy resistance in gastric adenocarcinoma. This study was conducted to clarify the role of E2F6 and RhoA, components of the Wnt signaling pathway, and SMUG1, a component of the BER pathway in gastric adenocarcinoma. Expression levels and clinicopathological significance of three biomarkers, namely E2F6, RhoA, and SMUG1, as potential signaling molecules involved in tumorigenesis and aggressive behavior, were examined using tissue microarray...
December 1, 2016: Clinical and Experimental Medicine
https://www.readbyqxmd.com/read/27908783/lipid-peroxidation-in-face-of-dna-damage-dna-repair-and-other-cellular-processes
#2
Barbara Tudek, Daria Zdżalik-Bielecka, Agnieszka Tudek, Konrad Kosicki, Anna Fabisiewicz, Elżbieta Speina
Exocyclic adducts to DNA bases are formed as a consequence of exposure to certain environmental carcinogens as well as inflammation and lipid peroxidation (LPO). Complex family of LPO products gives rise to a variety of DNA adducts, which can be grouped in two classes: (i) small etheno-type adducts of strong mutagenic potential, and (ii) bulky, propano-type adducts, which block replication and transcription, and are lethal lesions. Etheno-DNA adducts are removed from the DNA by base excision repair (BER), AlkB and nucleotide incision repair enzymes (NIR), while substituted propano-type lesions by nucleotide excision repair (NER) and homologous recombination (HR)...
November 28, 2016: Free Radical Biology & Medicine
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/27886261/neil3-induced-neurogenesis-protects-against-prion-disease-during-the-clinical-phase
#6
Clara M O Jalland, Katja Scheffler, Sylvie L Benestad, Torfinn Moldal, Cecilie Ersdal, Gjermund Gunnes, Rajikala Suganthan, Magnar Bjørås, Michael A Tranulis
Base excision repair (BER) is the major pathway for repair of oxidative DNA damage. Mice with genetic knockout of the BER enzyme Neil3 display compromised neurogenesis in the sub-ventricular zone of the lateral ventricle and sub-granular layer of the dentate gyrus of the hippocampus. To elucidate the impact of oxidative DNA damage-induced neurogenesis on prion disease we applied the experimental prion disease model on Neil3-deficient mice. The incubation period for the disease was similar in both wild type and Neil3(-/-) mice and the overall neuropathology appeared unaffected by Neil3 function...
November 25, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27880870/formation-and-processing-of-dna-damage-substrates-for-the-hneil-enzymes
#7
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/27870262/the-role-of-base-excision-repair-in-pathogenesis-of-breast-cancer-in-the-polish-population
#8
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/27866211/single-nucleotide-polymorphisms-of-genes-involved-in-repair-of-oxidative-dna-damage-and-the-risk-of-recurrent-depressive-disorder
#9
Piotr Czarny, Dominik Kwiatkowski, Monika Toma, Piotr Gałecki, Agata Orzechowska, Kinga Bobińska, Anna Bielecka-Kowalska, Janusz Szemraj, Michael Berk, George Anderson, Tomasz Śliwiński
BACKGROUND Depressive disorder, including recurrent type (rDD), is accompanied by increased oxidative stress and activation of inflammatory pathways, which may induce DNA damage. This thesis is supported by the presence of increased levels of DNA damage in depressed patients. Such DNA damage is repaired by the base excision repair (BER) pathway. BER efficiency may be influenced by polymorphisms in BER-related genes. Therefore, we genotyped nine single-nucleotide polymorphisms (SNPs) in six genes encoding BER proteins...
November 20, 2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/27865982/hide-and-seek-how-do-dna-glycosylases-locate-oxidatively-damaged-dna-bases-amidst-a-sea-of-undamaged-bases
#10
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/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/27836324/the-major-arabidopsis-thaliana-apurinic-apyrimidinic-endonuclease-arp-is-involved-in-the-plant-nucleotide-incision-repair-pathway
#12
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/27818579/visualizing-the-search-for-radiation-damaged-dna-bases-in-real-time
#13
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/27818219/removal-of-oxidatively-generated-dna-damage-by-overlapping-repair-pathways
#14
REVIEW
Vladimir Shafirovich, Nicholas E Geacintov
It is generally believed that the mammalian nucleotide excision repair pathway removes DNA helix-distorting bulky DNA lesions, while small non-bulky lesions are repaired by base excision repair (BER). However, recent work demonstrates that the oxidativly generated guanine oxidation products, spiroimininodihydantoin (Sp), 5-guanidinohydantoin (Gh), and certain intrastrand cross-linked lesions, are good substrates of NER and BER pathways that compete with one another in human cell extracts. The oxidation of guanine by peroxynitrite is known to generate 5-guanidino-4-nitroimidazole (NIm) which is structurally similar to Gh, except that the 4-nitro group in NIm is replaced by a keto group in Gh...
November 4, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27818081/enhanced-sensitivity-of-neil1-mice-to-chronic-uvb-exposure
#15
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/27803034/comparison-of-the-dna-damage-response-in-beas-2b-and-a549-cells-exposed-to-titanium-dioxide-nanoparticles
#16
M Biola-Clier, D Beal, S Caillat, S Libert, L Armand, N Herlin-Boime, S Sauvaigo, T Douki, M Carriere
For some decades production of titanium dioxide nanoparticle (TiO2-NP) has been increasing at a considerable rate; concerns as to the toxicity of these particles upon inhalation have been raised. Indeed, TiO2-NPs have been shown to induce significant genotoxicity and to adversely affect both major DNA repair mechanisms: base excision repair (BER) and nucleotide excision repair (NER). The aims of the present study were to (i) compare the genotoxicity of TiO2-NPs and their impact on DNA repair processes on A549 alveolar carcinoma and BEAS-2B normal bronchial lung cell lines and (ii) delve deeper into the mechanisms leading to these effects...
November 1, 2016: Mutagenesis
https://www.readbyqxmd.com/read/27794043/regulation-of-oxidized-base-damage-repair-by-chromatin-assembly-factor-1-subunit-a
#17
Chunying Yang, Shiladitya Sengupta, Pavana M Hegde, Joy Mitra, Shuai Jiang, Brooke Holey, Altaf H Sarker, Miaw-Sheue Tsai, Muralidhar L Hegde, Sankar Mitra
Reactive oxygen species (ROS), generated both endogenously and in response to exogenous stress, induce point mutations by mis-replication of oxidized bases and other lesions in the genome. Repair of these lesions via base excision repair (BER) pathway maintains genomic fidelity. Regulation of the BER pathway for mutagenic oxidized bases, initiated by NEIL1 and other DNA glycosylases at the chromatin level remains unexplored. Whether single nucleotide (SN)-BER of a damaged base requires histone deposition or nucleosome remodeling is unknown, unlike nucleosome reassembly which is shown to be required for other DNA repair processes...
October 27, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27788149/transcriptional-profiling-of-egg-allergy-and-relationship-to-disease-phenotype
#18
Roman Kosoy, Charuta Agashe, Alexander Grishin, Donald Y Leung, Robert A Wood, Scott H Sicherer, Stacie M Jones, A Wesley Burks, Wendy F Davidson, Robert W Lindblad, Peter Dawson, Miriam Merad, Brian A Kidd, Joel T Dudley, Hugh A Sampson, M Cecilia Berin
BACKGROUND: Egg allergy is one of the most common food allergies of childhood. There is a lack of information on the immunologic basis of egg allergy beyond the role of IgE. OBJECTIVE: To use transcriptional profiling as a novel approach to uncover immunologic processes associated with different phenotypes of egg allergy. METHODS: Peripheral blood mononuclear cells (PBMCs) were obtained from egg-allergic children who were defined as reactive (BER) or tolerant (BET) to baked egg, and from food allergic controls (AC) who were egg non-allergic...
2016: PloS One
https://www.readbyqxmd.com/read/27777312/mbd4-facilitates-immunoglobulin-class-switch-recombination
#19
Fernando Grigera, Robert Wuerffel, Amy L Kenter
Immunoglobulin heavy chain class switch recombination (CSR) requires targeted formation of DNA double strand breaks (DSBs) in repetitive switch region elements followed by ligation between distal breaks. The introduction of DSBs is initiated by activation induced cytidine deaminase (AID) and requires base excision repair (BER) and mismatch repair (MMR). The BER enzyme, methyl CpG binding domain protein 4 (MBD4) has been linked to the MMR pathway through its interaction with MutL homologue 1 (MLH1). We find that when the Mbd4 exons 6-8 are deleted in a switching B cell line DSB formation is severely reduced and CSR frequency is impaired...
October 24, 2016: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/27763529/polymorphism-of-the-xrcc1-gene-is-associated-with-susceptibility-and-short-term-recovery-of-ischemic-stroke
#20
Wei He, Peng Huang, Dinghua Liu, Lingling Zhong, Rongbin Yu, Jianan Li
Background: Base excision repair (BER) is the primary DNA repair system with the ability to fix base lesions caused by oxidative damage. Genetic variants influencing the BER pathway may affect the susceptibility and the outcomes of ischemic stroke. Here, we examined how single nucleotide polymorphisms (SNPs) associated with BER impact susceptibility and short-term recovery of ischemic stroke. Methods: We selected 320 ischemic stroke patients and 303 controls. Then we genotyped SNPs of NEIL1 rs4462560, NEIL3 rs12645561 and XRCC1 rs25487 in both groups...
October 17, 2016: International Journal of Environmental Research and Public Health
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