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DNA glycosylases

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https://www.readbyqxmd.com/read/28228863/medulloblastoma-and-ependymoma-cells-display-increased-levels-of-5-carboxylcytosine-and-elevated-tet1-expression
#1
Ashley Ramsawhook, Lara Lewis, Beth Coyle, Alexey Ruzov
BACKGROUND: Alteration of DNA methylation (5-methylcytosine, 5mC) patterns represents one of the causes of tumorigenesis and cancer progression. Tet proteins can oxidise 5mC to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine and 5-carboxylcytosine (5caC). Although the roles of these oxidised forms of 5mC (oxi-mCs) in cancer pathogenesis are still largely unknown, there are indications that they may be involved in the mechanisms of malignant transformation. Thus, reduction of 5hmC content represents an epigenetic hallmark of human tumours, and according to our recent report, 5caC is enriched in a proportion of breast cancers and gliomas...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28219007/electrochemistry-of-the-4fe4s-cluster-in-base-excision-repair-proteins-tuning-the-redox-potential-with-dna
#2
Phillip Leon Bartels, Andy Zhou, Anna Ruth Arnold, Nicole N Nunez, Frank Nelson Crespilho, Sheila S David, Jacqueline K Barton
Escherichia coli Endonuclease III (EndoIII) and MutY are DNA glycosylases that contain [4Fe4S] clusters and that serve to maintain the integrity of the genome after oxidative stress. Electrochemical studies on highly-oriented pyrolytic graphite (HOPG) revealed that DNA binding by EndoIII leads to a large negative shift in midpoint potential of the cluster, consistent with stabilization of the oxidized [4Fe4S]3+ form. However, the smooth, hydrophobic HOPG surface is non-ideal for working with proteins in the absence of DNA...
February 20, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/28209050/-active-photoprotection-sunscreens-with-dna-repair-enzymes-a-review-of-the-literature
#3
Matteo Megna, Serena Lembo, Nicola Balato, Giuseppe Monfrecola
Ultraviolet (UV) radiation exerts different harmful effects on human health, being the main etiological agents of certain skin cancers and photoaging. In this context, photoprotection, intended as a set of measures adopted to limit and prevent the effects of UV radiation, plays a critical role in avoiding undesired sunlight outcomes. Traditional sunscreens represent a widely used photoprotective approach, even if they exert a "passive photoprotection" and are not effective once damage to skin cells has been generated after sun exposure...
February 16, 2017: Giornale Italiano di Dermatologia e Venereologia: Organo Ufficiale, Società Italiana di Dermatologia e Sifilografia
https://www.readbyqxmd.com/read/28202616/dna-repair-interacts-with-autophagy-to-regulate-inflammatory-responses-to-pulmonary-hyperoxia
#4
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/28199314/whole-genome-landscape-of-pancreatic-neuroendocrine-tumours
#5
Aldo Scarpa, David K Chang, Katia Nones, Vincenzo Corbo, Ann-Marie Patch, Peter Bailey, Rita T Lawlor, Amber L Johns, David K Miller, Andrea Mafficini, Borislav Rusev, Maria Scardoni, Davide Antonello, Stefano Barbi, Katarzyna O Sikora, Sara Cingarlini, Caterina Vicentini, Skye McKay, Michael C J Quinn, Timothy J C Bruxner, Angelika N Christ, Ivon Harliwong, Senel Idrisoglu, Suzanne McLean, Craig Nourse, Ehsan Nourbakhsh, Peter J Wilson, Matthew J Anderson, J Lynn Fink, Felicity Newell, Nick Waddell, Oliver Holmes, Stephen H Kazakoff, Conrad Leonard, Scott Wood, Qinying Xu, Shivashankar Hiriyur Nagaraj, Eliana Amato, Irene Dalai, Samantha Bersani, Ivana Cataldo, Angelo P Dei Tos, Paola Capelli, Maria Vittoria Davì, Luca Landoni, Anna Malpaga, Marco Miotto, Vicki L J Whitehall, Barbara A Leggett, Janelle L Harris, Jonathan Harris, Marc D Jones, Jeremy Humphris, Lorraine A Chantrill, Venessa Chin, Adnan M Nagrial, Marina Pajic, Christopher J Scarlett, Andreia Pinho, Ilse Rooman, Christopher Toon, Jianmin Wu, Mark Pinese, Mark Cowley, Andrew Barbour, Amanda Mawson, Emily S Humphrey, Emily K Colvin, Angela Chou, Jessica A Lovell, Nigel B Jamieson, Fraser Duthie, Marie-Claude Gingras, William E Fisher, Rebecca A Dagg, Loretta M S Lau, Michael Lee, Hilda A Pickett, Roger R Reddel, Jaswinder S Samra, James G Kench, Neil D Merrett, Krishna Epari, Nam Q Nguyen, Nikolajs Zeps, Massimo Falconi, Michele Simbolo, Giovanni Butturini, George Van Buren, Stefano Partelli, Matteo Fassan, Kum Kum Khanna, Anthony J Gill, David A Wheeler, Richard A Gibbs, Elizabeth A Musgrove, Claudio Bassi, Giampaolo Tortora, Paolo Pederzoli, John V Pearson, Nicola Waddell, Andrew V Biankin, Sean M Grimmond
The diagnosis of pancreatic neuroendocrine tumours (PanNETs) is increasing owing to more sensitive detection methods, and this increase is creating challenges for clinical management. We performed whole-genome sequencing of 102 primary PanNETs and defined the genomic events that characterize their pathogenesis. Here we describe the mutational signatures they harbour, including a deficiency in G:C > T:A base excision repair due to inactivation of MUTYH, which encodes a DNA glycosylase. Clinically sporadic PanNETs contain a larger-than-expected proportion of germline mutations, including previously unreported mutations in the DNA repair genes MUTYH, CHEK2 and BRCA2...
February 15, 2017: Nature
https://www.readbyqxmd.com/read/28194454/in-vitro-genotoxicity-of-carcinogenic-asarone-isomers
#6
S Haupenthal, K Berg, M Gründken, S Vallicotti, M Hemgesberg, K Sak, D Schrenk, M Esselen
The present study focused on genotoxic properties of the carcinogenic phenylpropanoids α-asarone and β-asarone, which are found in several herbs and spices, such as Acorus calamus or Acorus gramineus. Cytotoxic and genotoxic effects were determined in human liver carinoma HepG2 cells, in hamster lung fibroblast V79 cells and in human cytochrome P450 1A2 and human sulfotransferase 1C2 transfected V79 cells (tV79). The Alamar blue assay was used to measure cytotoxicity of both isomers prior to the identification of DNA damaging properties by single cell gel electrophoresis (comet assay)...
February 14, 2017: Food & Function
https://www.readbyqxmd.com/read/28161308/sensitive-detection-of-dna-oxidation-damage-induced-by-nanomaterials
#7
REVIEW
Andrew Collins, Naouale El Yamani, Maria Dusinska
From a toxicological point of view, nanomaterials are of interest; because - on account of their great surface area relative to mass - they tend to be more reactive than the bulk chemicals from which they are derived. They might in some cases have the potential to damage DNA directly, or could act via the induction of oxidative stress. The comet assay (single cell gel electrophoresis) is widely used to measure DNA strand breaks and also oxidised bases, by including in the procedure digestion with lesion-specific enzymes such as formamidopyrimidine DNA glycosylase (which converts oxidised purines to breaks) or endonuclease III (recognising oxidised pyrimidines)...
February 2, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28159613/the-vaccinia-virus-dna-polymerase-and-its-processivity-factor
#8
REVIEW
Maciej W Czarnecki, Paula Traktman
Vaccinia virus is the prototypic poxvirus. The 192 kilobase double-stranded DNA viral genome encodes most if not all of the viral replication machinery. The vaccinia virus DNA polymerase is encoded by the E9L gene. Sequence analysis indicates that E9 is a member of the B family of replicative polymerases. The enzyme has both polymerase and 3'-5' exonuclease activities, both of which are essential to support viral replication. Genetic analysis of E9 has identified residues and motifs whose alteration can confer temperature-sensitivity, drug resistance (phosphonoacetic acid, aphidicolin, cytosine arabinsode, cidofovir) or altered fidelity...
February 1, 2017: Virus Research
https://www.readbyqxmd.com/read/28150947/sequencing-the-mouse-genome-for-the-oxidatively-modified-base-8-oxo-7-8-dihydroguanine-by-og-seq
#9
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/28143930/oxidative-dna-damage-is-epigenetic-by-regulating-gene-transcription-via-base-excision-repair
#10
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/28130550/control-of-demeter-dna-demethylase-gene-transcription-in-male-and-female-gamete-companion-cells-in-arabidopsis-thaliana
#11
Jin-Sup Park, Jennifer M Frost, Kyunghyuk Park, Hyonhwa Ohr, Guen Tae Park, Seohyun Kim, Hyunjoo Eom, Ilha Lee, Janie S Brooks, Robert L Fischer, Yeonhee Choi
The DEMETER (DME) DNA glycosylase initiates active DNA demethylation via the base-excision repair pathway and is vital for reproduction in Arabidopsis thaliana DME-mediated DNA demethylation is preferentially targeted to small, AT-rich, and nucleosome-depleted euchromatic transposable elements, influencing expression of adjacent genes and leading to imprinting in the endosperm. In the female gametophyte, DME expression and subsequent genome-wide DNA demethylation are confined to the companion cell of the egg, the central cell...
January 27, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28130451/structural-basis-for-the-lesion-scanning-mechanism-of-the-bacterial-muty-dna-glycosylase
#12
Lan Wang, Srinivas Chakravarthy, Gregory L Verdine
The highly mutagenic A:oxoG (8-oxoguanine) base-pair is generated mainly by misreplication of the C:oxoG base-pair, the oxidation product of the C:G base-pair. A:oxoG base-pair is particularly insidious because neither base in it carries faithful information to direct the repair of the other. The bacterial MutY (MUTYH in humans) adenine DNA glycosylase is able to initiate the repair of A:oxoG by selectively cleaving the A base from the A:oxoG base-pair. The difference between faithful repair and wreaking mutagenic havoc on the genome lies in the accurate discrimination between two structurally similar base-pairs: A:oxoG and A:T...
January 27, 2017: Journal of Biological Chemistry
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
#13
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/28118378/dna-polymerases-imuc-and-dinb-are-involved-in-dna-alkylation-damage-tolerance-in-pseudomonas-aeruginosa-and-pseudomonas-putida
#14
Tatjana Jatsenko, Julia Sidorenko, Signe Saumaa, Maia Kivisaar
Translesion DNA synthesis (TLS), facilitated by low-fidelity polymerases, is an important DNA damage tolerance mechanism. Here, we investigated the role and biological function of TLS polymerase ImuC (former DnaE2), generally present in bacteria lacking DNA polymerase V, and TLS polymerase DinB in response to DNA alkylation damage in Pseudomonas aeruginosa and P. putida. We found that TLS DNA polymerases ImuC and DinB ensured a protective role against N- and O-methylation induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in both P...
2017: PloS One
https://www.readbyqxmd.com/read/28110804/differential-role-of-base-excision-repair-proteins-in-mediating-cisplatin-cytotoxicity
#15
Akshada Sawant, Ashley M Floyd, Mohan Dangeti, Wen Lei, Robert W Sobol, Steve M Patrick
Interstrand crosslinks (ICLs) are covalent lesions formed by cisplatin. The mechanism for the processing and removal of ICLs by DNA repair proteins involves nucleotide excision repair (NER), homologous recombination (HR) and fanconi anemia (FA) pathways. In this report, we monitored the processing of a flanking uracil adjacent to a cisplatin ICL by the proteins involved in the base excision repair (BER) pathway. Using a combination of extracts, purified proteins, inhibitors, functional assays and cell culture studies, we determined the specific BER proteins required for processing a DNA substrate with a uracil adjacent to a cisplatin ICL...
January 11, 2017: DNA Repair
https://www.readbyqxmd.com/read/28107710/in-vivo-assesment-of-the-genotoxic-and-oxidative-stress-effects-of-particulate-matter-on-echinogammarus-veneris
#16
Melissa Marcoccia, Lucilla Ronci, Elvira De Matthaeis, Andrea Setini, Cinzia Perrino, Silvia Canepari
Seven types of atmospheric dusts (road dust, soil dust, brake dust, desert dust, pellet ash and coke and certified material NIST1648a - urban dust) have been tested for their genotoxicity on specimens of Echinogammarus veneris, a small aquatic amphipod. Experiments were carried out in vivo, by exposing the animals for 24 h to water containing 25 mg/L of dust. Each dust has been chemically analyzed for ions, elemental carbon, organic carbon and for the soluble and insoluble fractions of elements. Non-specific damages to DNA have been evaluated by the comet test, while oxidative damages have been estimated by coupling the comet test with formamido pyrimidine DNA glycosylase reaction...
January 6, 2017: Chemosphere
https://www.readbyqxmd.com/read/28106786/sulfolobus-acidocaldarius-udg-can-remove-du-from-the-rna-backbone-insight-into-the-specific-recognition-of-uracil-linked-with-deoxyribose
#17
Gang-Shun Yi, Wei-Wei Wang, Wei-Guo Cao, Feng-Ping Wang, Xi-Peng Liu
Sulfolobus acidocaldarius encodes family 4 and 5 uracil-DNA glycosylase (UDG). Two recombinant S. acidocaldarius UDGs (SacUDG) were prepared and biochemically characterized using oligonucleotides carrying a deaminated base. Both SacUDGs can remove deoxyuracil (dU) base from both double-stranded DNA and single-stranded DNA. Interestingly, they can remove U linked with deoxyribose from single-stranded RNA backbone, suggesting that the riboses on the backbone have less effect on the recognition of dU and hydrolysis of the C-N glycosidic bond...
January 18, 2017: Genes
https://www.readbyqxmd.com/read/28098999/dna-deformation-coupled-recognition-of-8-oxoguanine-conformational-kinetic-gating-in-human-dna-glycosylase
#18
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/28098985/hmgb1-stimulates-activity-of-polymerase-%C3%AE-on-nucleosome-substrates
#19
Angela Balliano, Fanfan Hao, Catherine Njeri, Lata Balakrishnan, Jeffrey J Hayes
The process of base excision repair (BER) recognizes and repairs small lesions or inappropriate bases on DNA through either a short-patch or long-patch pathway. The enzymes involved in BER have been well-characterized on DNA substrates, and, somewhat surprisingly, many of these enzymes, including several DNA glycosylases, AP endonuclease (APE), FEN1 endonuclease, and DNA ligases, have been shown to have activity on DNA substrates within nucleosomes. DNA polymerase β (Pol β), however, exhibits drastically reduced or no activity on nucleosomal DNA...
January 18, 2017: Biochemistry
https://www.readbyqxmd.com/read/28098352/dna-repair-and-erasure-of-5-methylcytosine-in-vertebrates
#20
Lars Schomacher, Christof Niehrs
DNA methylation plays important roles in development and disease. Yet, only recently has the dynamic nature of this epigenetic mark via oxidation and DNA repair-mediated demethylation been recognized. A major conceptual challenge to the model that DNA methylation is reversible is the risk of genomic instability, which may come with widespread DNA repair activity. Here, we focus on recent advances in mechanisms of TET-TDG mediated demethylation and cellular strategies that avoid genomic instability. We highlight the recently discovered involvement of NEIL DNA glycosylases, which cooperate with TDG in oxidative demethylation to accelerate substrate turnover and promote the organized handover of harmful repair intermediates to maintain genome stability...
January 18, 2017: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
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