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DNA glycosylases

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https://www.readbyqxmd.com/read/29149600/repair-of-uv-induced-dna-damage-independent-of-nucleotide-excision-repair-is-masked-by-mutyh
#1
Abdelghani Mazouzi, Federica Battistini, Sarah C Moser, Joana Ferreira da Silva, Marc Wiedner, Michel Owusu, Charles-Hugues Lardeau, Anna Ringler, Beatrix Weil, Jürgen Neesen, Modesto Orozco, Stefan Kubicek, Joanna I Loizou
DNA lesions caused by UV damage are thought to be repaired solely by the nucleotide excision repair (NER) pathway in human cells. Patients carrying mutations within genes functioning in this pathway display a range of pathologies, including an increased susceptibility to cancer, premature aging, and neurological defects. There are currently no curative therapies available. Here we performed a high-throughput chemical screen for agents that could alleviate the cellular sensitivity of NER-deficient cells to UV-induced DNA damage...
November 16, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29148771/an-qm-mm-study-of-the-reaction-catalyzed-by-alkyladenine-dna-glycosylase-examination-of-the-substrate-specificity-of-a-dna-repair-enzyme
#2
Stefan A P Lenz, Stacey D Wetmore
Human alkyladenine DNA glycosylase (AAG) functions as part of the base excision repair pathway to excise structurally diverse oxidized and alkylated DNA purines. Specifically, AAG uses a water molecule activated by a general base and a non-specific active site lined with aromatic residues to cleave the N-glycosidic bond. Despite broad substrate specificity, AAG does not target the natural purines (adenine (A) and guanine (G)). Using the ONIOM(QM:MM) methodology, we provide fundamental atomic level details of AAG bound to DNA-containing a neutral substrate (hypoxanthine (Hx)), a non-substrate (G), or a cationic substrate (7-methylguanine (7MeG)), and probe changes in the reaction pathway that occur when AAG targets different nucleotides...
November 17, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/29137710/loop-mediated-isothermal-amplification-using-self-avoiding-molecular-recognition-systems-and-antarctic-thermal-sensitive-uracil-dna-glycosylase-for-detection-of-nucleic-acid-with-prevention-of-carryover-contamination
#3
Yi Wang, Dongxin Liu, Jianping Deng, Yan Wang, Jianguo Xu, Changyun Ye
Loop-mediated isothermal amplification (LAMP) is the most popular technique to amplify nucleic acid sequence without the use of temperature cycling. However, LAMP is often confounded by false-positive results, arising from interactions between (hetero-dimer) or within (self-dimerization) primers, off-target hybrids and carryover contaminants. Here, we devised a new LAMP technique that is self-avoiding molecular recognition system (SAMRS) components and antarctic thermal sensitive uracil-DNA-glycosylase (AUDG) enzyme-assisted, termed AUDG-SAMRS-LAMP...
December 15, 2017: Analytica Chimica Acta
https://www.readbyqxmd.com/read/29132233/prospects-for-modulating-the-cd40-cd40l-pathway-in-the-therapy-of-the-hyper-igm-syndrome
#4
Xiangxue Meng, Bin Yang, Wen-Chen Suen
The critical role of the CD40/CD40L pathway in B-cell proliferation, immunoglobulin (Ig) isotype switching and germinal center formation has been studied and described extensively in previous literature. Interruption of the CD40/CD40L signal causes hyper-IgM (HIGM) syndrome, which has been classified and recognized as a group of rare inherited immune deficiency disorders. Defects in CD40 and CD40L interactions or in downstream signaling molecules, including activation-induced cytidine deaminase, uracyl-DNA-glycosylase, NF-κB and DNA repair enzymes, result in an increased level of serum IgM and a significantly decreased or absent level of IgA, IgG and IgE that is accompanied by severe recurrent infections and autoimmune diseases...
January 1, 2017: Innate Immunity
https://www.readbyqxmd.com/read/29122935/in-vivo-measurements-of-interindividual-differences-in-dna-glycosylases-and-ape1-activities
#5
Isaac A Chaim, Zachary D Nagel, Jennifer J Jordan, Patrizia Mazzucato, Le P Ngo, Leona D Samson
The integrity of our DNA is challenged with at least 100,000 lesions per cell on a daily basis. Failure to repair DNA damage efficiently can lead to cancer, immunodeficiency, and neurodegenerative disease. Base excision repair (BER) recognizes and repairs minimally helix-distorting DNA base lesions induced by both endogenous and exogenous DNA damaging agents. Levels of BER-initiating DNA glycosylases can vary between individuals, suggesting that quantitating and understanding interindividual differences in DNA repair capacity (DRC) may enable us to predict and prevent disease in a personalized manner...
November 9, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29121049/haplotype-cgc-from-xpd-hogg1-and-itga2-polymorphisms-increases-the-risk-of-nasopharyngeal-carcinoma-in-malaysia
#6
Eng-Zhuan Ban, Munn-Sann Lye, Pei Pei Chong, Yoke-Yeow Yap, Siew Ying Crystale Lim, Hejar Abdul Rahman
BACKGROUND: 8-oxoG, a common DNA lesion resulting from reactive oxygen species (ROS), has been shown to be associated with cancer initiation. hOGG1 DNA glycosylase is the primary enzyme responsible for excision of 8-oxoG through base excision repair (BER). Integrins are members of a family of cell surface receptors that mediate the cell-cell and extracellular matrix (ECM) interactions. Integrins are involved in almost every aspect of carcinogenesis, from cell differentiation, cell proliferation, metastasis to angiogenesis...
2017: PloS One
https://www.readbyqxmd.com/read/29118522/association-of-leukotrichia-in-vitiligo-and-asp148glu-polymorphism-of-apurinic-apyrimidinic-endonuclease-1
#7
A Fatih Aydin, İkbal Esen Aydıngöz, Semra Doğru-Abbasoğlu, Pervin Vural, Müjdat Uysal
Background: Oxidative stress and increased DNA damage have been implicated in the etiopathogenesis of vitiligo. Oxidative DNA damage is mainly repaired by the base excision repair (BER) pathway. Aim: We sought to determine whether polymorphisms in DNA repair genes may have a role in the pathogenesis of vitiligo. Materials and Methods: We conducted a study including 100 patients with vitiligo and age- and sex-matched 193 control subjects to examine the role of single-nucleotide polymorphisms of BER genes, human 8-oxoG DNA N-glycosylase 1 (codon 326), apurinic/apyrimidinic endonuclease 1 (APE1) (codon 148), and X-ray repair cross-complementing group 1 (codon 399) as risk factors for vitiligo...
October 2017: International Journal of Trichology
https://www.readbyqxmd.com/read/29117941/loss-of-uracil-dna-glycosylase-selectively-re-sensitizes-p53-mutant-and-deficient-cells-to-5-fdu
#8
Yan Yan, Yulan Qing, John J Pink, Stanton L Gerson
Thymidylate synthase (TS) inhibitors including fluoropyrimidines [e.g., 5-Fluorouracil (5-FU) and 5-Fluorodeoxyuridine (5-FdU, floxuridine)] and antifolates (e.g., pemetrexed) are widely used against solid tumors. Previously, we reported that shRNA-mediated knockdown (KD) of uracil DNA glycosylase (UDG) sensitized cancer cells to 5-FdU. Since p53 has also been shown as a critical determinant of the sensitivity to TS inhibitors, we further interrogated 5-FdU cytotoxicity after UDG depletion with regard to p53 status...
November 8, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29108254/the-impacts-of-genetic-polymorphisms-in-genes-of-base-excision-repair-pathway-on-the-efficacy-and-acute-toxicities-of-chemo-radiotherapy-in-patients-with-nasopharyngeal-carcinoma
#9
Jing Wang, Chengxian Guo, Xiaochang Gong, Fan Ao, Yuling Huang, Lihua Huang, Yiqiang Tang, Chunling Jiang, Xiaoxue Xie, Qing Dong, Min Huang, Jingao Li
Purpose: To explore whether polymorphisms in base excision repair (BER) pathway genes are predictors of (chemo)radiotherapy outcome in patients with nasopharyngeal carcinoma (NPC). Methods: We genotyped five potentially functional single nucleotide polymorphisms (SNPs) of three genes in the BER pathway in 174 NPC patients who were treated with (chemo)radiotherapy. Sequenom MassArray was used for SNPs analysis. The efficacy at the end of radiotherapy and at 3 months after radiotherapy was evaluated by Response Evaluation Criteria in Solid Tumors (RECIST)...
October 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29105096/nthl1-and-mutyh-polyposis-syndromes-two-sides-of-the-same-coin
#10
REVIEW
Robbert D A Weren, Marjolijn J L Ligtenberg, Ad Geurts van Kessel, Richarda M De Voer, Nicoline Hoogerbrugge, Roland P Kuiper
It is well-established now that germline genomic aberrations can underlie high-penetrant familial polyposis and colorectal cancer syndromes, but a genetic cause has not yet been found for the major proportion of patients with polyposis. Since next generation sequencing has become widely accessible, several novel, but rare, high-penetrant risk factors for adenomatous polyposis have been identified, all operating in pathways responsible for genomic maintenance and DNA repair. One of these is the base excision repair (BER) pathway...
November 3, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/29101721/restoration-of-cognitive-performance-in-mice-carrying-a-deficient-allele-of-8-oxoguanine-dna-glycosylase-by-x-ray-irradiation
#11
Tim Hofer, Nur Duale, Martine Muusse, Dag Marcus Eide, Hildegunn Dahl, Fernando Boix, Jannike M Andersen, Ann Karin Olsen, Oddvar Myhre
Environmental stressors inducing oxidative stress such as ionizing radiation may influence cognitive function and neuronal plasticity. Recent studies have shown that transgenic mice deficient of DNA glycosylases display unexpected cognitive deficiencies related to changes in gene expression in the hippocampus. The main objectives of the present study were to determine learning and memory performance in C57BL/6NTac 8-oxoguanine DNA glycosylase 1 (Ogg1)(+/-) (heterozygote) and Ogg1(+/+) (wild type, WT) mice, to study whether a single acute X-ray challenge (0...
November 3, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/29100183/microcystin-lr-increases-genotoxicity-induced-by-aflatoxin-b1-through-oxidative-stress-and-dna-base-excision-repair-genes-in-human-hepatic-cell-lines
#12
Wenyi Liu, Lingqiao Wang, Chuanfen Zheng, Lebin Liu, Jia Wang, Daibo Li, Yao Tan, Xilong Zhao, Lixiong He, Weiqun Shu
Aflatoxin B1 (AFB1) and microcystin-LR (MC-LR) simultaneously exist in polluted food and water in humid and warm areas, and each has been reported to be genotoxic to liver and associated with hepatocellular carcinoma (HCC). However, the genotoxic effects of the two biotoxins in combination and potential mechanism remain unknown. We treated the human hepatic cell line HL7702 with AFB1 and MC-LR together at different ratios, examined their genotoxic effects using micronuclei and comet assays, and evaluated the possible mechanism by measuring oxidative stress markers and DNA base excision repair (BER) genes...
October 31, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/29099587/combining-h-d-exchange-mass-spectrometry-and-computational-docking-to-derive-the-structure-of-protein-protein-complexes
#13
Victoria A Roberts, Michael E Pique, Simon Hsu, Sheng Li
Protein-protein interactions are essential for biological function, but structures of protein-protein complexes are difficult to obtain experimentally. To derive the protein complex of the DNA-repair enzyme human uracil-DNA-glycosylase (hUNG) with its protein inhibitor (UGI), we combined rigid-body computational docking with hydrogen/deuterium exchange mass spectrometry (DXMS). Computational docking of the unbound protein structures provides a list of possible three-dimensional models of the complex; DXMS identifies solvent-protected protein residues...
November 16, 2017: Biochemistry
https://www.readbyqxmd.com/read/29098062/mutation-spectrum-induced-by-8-bromoguanine-a-base-damaged-by-reactive-brominating-species-in-human-cells
#14
Kazuya Shinmura, Hisami Kato, Masanori Goto, Hong Tao, Yusuke Inoue, Satoki Nakamura, Haruki Yoshida, Emi Tsuzaki, Haruhiko Sugimura
To date, the types of mutations caused by 8-bromoguanine (8BrG), a major base lesion induced by reactive brominating species during inflammation, in human cells and the 8BrG repair system remain largely unknown. In this study, we performed a supF forward mutation assay using a shuttle vector plasmid containing a single 8BrG in three kinds of human cell lines and revealed that 8BrG in DNA predominantly induces a G → T mutation but can also induce G → C, G → A, and delG mutations in human cells...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29079575/hiv-1-vpr-protein-directly-loads-helicase-like-transcription-factor-hltf-onto-the-crl4-dcaf1-e3-ubiquitin-ligase
#15
Xiaohong Zhou, Maria Delucia, Caili Hao, Kasia Hrecka, Christina Monnie, Jacek Skowronski, Jinwoo Ahn
The Vpr protein is an accessory virulence factor of HIV-1 that facilitates infection in immune cells. Cellular functions of Vpr are tied to its interaction with DCAF1, a substrate receptor component of the CRL4 E3 ubiquitin ligase. Recent proteomic approaches suggested that Vpr degrades HLTF DNA helicase in a proteasome-dependent manner by redirecting the CRL4-DCAF1 E3 ligase. However, the precise molecular mechanism of Vprdependent HLTF depletion is not known. Here, using in vitro reconstitution assays, we show that Vpr mediates polyubiquitination of HLTF, by directly loading it onto the C-terminal WD40 domain of DCAF1 in complex with the CRL4 E3 ubiquitin ligase...
October 27, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29073080/maladaptive-dna-repair-is-the-ultimate-contributor-to-the-death-of-trimethoprim-treated-cells-under-aerobic-and-anaerobic-conditions
#16
Xavier Giroux, Wei-Lin Su, Marie-Florence Bredeche, Ivan Matic
The bactericidal effects of antibiotics are undoubtedly triggered by target-specific interactions, but there is growing evidence that an important aspect of cytotoxicity results from treatment-induced metabolic perturbations. In this study, we characterized molecular mechanisms whereby trimethoprim treatment results in cell death, using Escherichia coli as the model organism. E. coli cells grown in rich medium that contained all amino acids and low amounts of thymidine were treated with trimethoprim under aerobic and anaerobic conditions...
October 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29072685/sirt3-protects-hepatocytes-from-oxidative-injury-by-enhancing-ros-scavenging-and-mitochondrial-integrity
#17
Jingxin Liu, Dan Li, Tian Zhang, Qiang Tong, Richard Dequan Ye, Ligen Lin
Evidences of oxidative stress and mitochondrial dysfunction have been recognized in most of clinical and experimental liver diseases. SIRT3, a member of NAD(+)-dependent deacetylases, is mainly localized in mitochondria. So far, the role of SIRT3 in protecting hepatocytes against oxidative stress remains elusive. Herein, we found SIRT3 protein expression is decreased in tert-butyl hydroperoxide (t-BHP)-treated AML12 cells in vitro and primary hepatocytes from CCl4-injured mice in vivo. To further verify the role of SIRT3 in protecting hepatocytes from t-BHP-induced injury, SIRT3 overexpressed AML12 cell line and primary hepatocytes were generated...
October 26, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29054852/selective-base-excision-repair-of-dna-damage-by-the-non-base-flipping-dna-glycosylase-alkc
#18
Rongxin Shi, Elwood A Mullins, Xing-Xing Shen, Kori T Lay, Philip K Yuen, Sheila S David, Antonis Rokas, Brandt F Eichman
DNA glycosylases preserve genome integrity and define the specificity of the base excision repair pathway for discreet, detrimental modifications, and thus, the mechanisms by which glycosylases locate DNA damage are of particular interest. Bacterial AlkC and AlkD are specific for cationic alkylated nucleobases and have a distinctive HEAT-like repeat (HLR) fold. AlkD uses a unique non-base-flipping mechanism that enables excision of bulky lesions more commonly associated with nucleotide excision repair. In contrast, AlkC has a much narrower specificity for small lesions, principally N3-methyladenine (3mA)...
October 20, 2017: EMBO Journal
https://www.readbyqxmd.com/read/29051947/pre-steady-state-kinetic-analysis-of-damage-recognition-by-human-single-strand-selective-monofunctional-uracil-dna-glycosylase-smug1
#19
Alexandra A Kuznetsova, Danila A Iakovlev, Inna V Misovets, Alexander A Ishchenko, Murat K Saparbaev, Nikita A Kuznetsov, Olga S Fedorova
In all organisms, DNA glycosylases initiate base excision repair pathways resulting in removal of aberrant bases from DNA. Human SMUG1 belongs to the superfamily of uracil-DNA glycosylases catalyzing the hydrolysis of the N-glycosidic bond of uridine and uridine lesions bearing oxidized groups at C5: 5-hydroxymethyluridine (5hmU), 5-formyluridine (5fU), and 5-hydroxyuridine (5hoU). An apurinic/apyrimidinic (AP) site formed as the product of an N-glycosylase reaction is tightly bound to hSMUG1, thus inhibiting the downstream action of AP-endonuclease APE1...
October 20, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/29046123/differential-effects-of-silver-nanoparticles-on-dna-damage-and-dna-repair-gene-expression-in-ogg1-deficient-and-wild-type-mice
#20
Sameera Nallanthighal, Cadia Chan, Thomas M Murray, Aaron P Mosier, Nathaniel C Cady, Ramune Reliene
Due to extensive use in consumer goods, it is important to understand the genotoxicity of silver nanoparticles (AgNPs) and identify susceptible populations. 8-Oxoguanine DNA glycosylase 1 (OGG1) excises 8-oxo-7,8-dihydro-2-deoxyguanine (8-oxoG), a pro-mutagenic lesion induced by oxidative stress. To understand whether defects in OGG1 is a possible genetic factor increasing an individual's susceptibly to AgNPs, we determined DNA damage, genome rearrangements, and expression of DNA repair genes in Ogg1-deficient and wild type mice exposed orally to 4 mg/kg of citrate-coated AgNPs over a period of 7 d...
October 19, 2017: Nanotoxicology
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