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DNA glycosylases

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https://www.readbyqxmd.com/read/28318075/thymine-dna-glycosylase-modulates-dna-damage-response-and-gene-expression-by-base-excision-repair-dependent-and-independent-mechanisms
#1
Tomohumi Nakamura, Kouichi Murakami, Haruto Tada, Yoshihiko Uehara, Jumpei Nogami, Kazumitsu Maehara, Yasuyuki Ohkawa, Hisato Saitoh, Hideo Nishitani, Tetsuya Ono, Ryotaro Nishi, Masayuki Yokoi, Wataru Sakai, Kaoru Sugasawa
Thymine DNA glycosylase (TDG) is a base excision repair (BER) enzyme, which is implicated in correction of deamination-induced DNA mismatches, the DNA demethylation process and regulation of gene expression. Because of these pivotal roles associated, it is crucial to elucidate how the TDG functions are appropriately regulated in vivo. Here, we present evidence that the TDG protein undergoes degradation upon various types of DNA damage, including ultraviolet light (UV). The UV-induced degradation of TDG was dependent on proficiency in nucleotide excision repair and on CRL4(CDT)(2) -mediated ubiquitination that requires a physical interaction between TDG and DNA polymerase clamp PCNA...
March 20, 2017: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
https://www.readbyqxmd.com/read/28317990/cyclic-enzymatic-repairing-mediated-dual-signal-amplification-for-real-time-monitoring-of-thymine-dna-glycosylase
#2
Li-Juan Wang, Zi-Yue Wang, Qianyi Zhang, Bo Tang, Chun-Yang Zhang
We develop a new fluorescence method for real-time monitoring of thymine DNA glycosylase (TDG) activity through cyclic enzymatic repairing-mediated dual-signal amplification. This method exhibits excellent sensitivity with a detection limit of 5.6 × 10(-7) U μL(-1), and it can be used to determine kinetic parameters and quantify TDG activity from even single cancer cells.
March 20, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28314872/rt-qpcr-with-chimeric-du-stem-loop-primer-is-efficient-for-the-detection-of-bacterial-small-rnas
#3
Yangfan Wu, Xuejiao Xing, Ting You, Rubing Liang, Jianhua Liu
Small non-coding RNAs are considered be involved in the regulation of multiple cellular processes. Quantitative reverse transcription PCR (RT-qPCR) is widely used in the detection of eukaryotic microRNA, and the stem-loop primers can improve the specificity and efficiency of reverse transcription. However, the loop structure of primers probably influence the next quantitative amplification due to the base stacking and steric hindrance. Here, we designed a chimeric stem-loop primer with a deoxyuracil (dU) base located near the RNA matching part...
March 17, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28306242/excision-repair-initiated-enzyme-assisted-bicyclic-cascade-signal-amplification-for-ultrasensitive-detection-of-uracil-dna-glycosylase
#4
Li-Juan Wang, Ming Ren, Qianyi Zhang, Bo Tang, Chun-Yang Zhang
Uracil-DNA glycosylase (UDG) is an important base excision repair (BER) enzyme responsible for the repair of uracil-induced DNA lesion and the maintenance of genomic integrity, while the aberrant expression of UDG is associated with a variety of cancers. Thus the accurate detection of UDG activity is essential to biomedical research and clinical diagnosis. Here, we develop a fluorescent method for ultrasensitive detection of UDG activity using excision repair-initiated enzyme-assisted bicyclic cascade signal amplification...
March 17, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28292631/probing-the-activity-of-nthl1-orthologs-by-targeting-conserved-amino-acid-residues
#5
Susan M Robey-Bond, Meredith A Benson, Ramiro Barrantes-Reynolds, Jeffrey P Bond, Susan S Wallace
The base excision repair DNA glycosylases, EcoNth and hNTHL1, are homologous, with reported overlapping yet different substrate specificities. The catalytic amino acid residues are known and are identical between the two enzymes although the exact structures of the substrate binding pockets remain to be determined. We sought to explore the sequence basis of substrate differences using a phylogeny-based design of site-directed mutations. Mutations were made for each enzyme in the vicinity of the active site and we examined these variants for glycosylase and lyase activity...
March 6, 2017: DNA Repair
https://www.readbyqxmd.com/read/28283534/pms2-and-uracil-dna-glycosylases-act-jointly-in-the-mismatch-repair-pathway-to-generate-ig-gene-mutations-at-a-t-base-pairs
#6
Giulia Girelli Zubani, Marija Zivojnovic, Annie De Smet, Olivier Albagli-Curiel, François Huetz, Jean-Claude Weill, Claude-Agnès Reynaud, Sébastien Storck
During somatic hypermutation (SHM) of immunoglobulin genes, uracils introduced by activation-induced cytidine deaminase are processed by uracil-DNA glycosylase (UNG) and mismatch repair (MMR) pathways to generate mutations at G-C and A-T base pairs, respectively. Paradoxically, the MMR-nicking complex Pms2/Mlh1 is apparently dispensable for A-T mutagenesis. Thus, how detection of U:G mismatches is translated into the single-strand nick required for error-prone synthesis is an open question. One model proposed that UNG could cooperate with MMR by excising a second uracil in the vicinity of the U:G mismatch, but it failed to explain the low impact of UNG inactivation on A-T mutagenesis...
March 10, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28277978/targeted-dna-demethylation-in-human-cells-by-fusion-of-a-plant-5-methylcytosine-dna-glycosylase-to-a-sequence-specific-dna-binding-domain
#7
Jara Teresa Parrilla-Doblas, Rafael R Ariza, Teresa Roldán-Arjona
DNA methylation is a crucial epigenetic mark associated to gene silencing, and its targeted removal is a major goal of epigenetic editing. In animal cells, DNA demethylation involves iterative 5mC oxidation by TET enzymes followed by replication-dependent dilution and/or replication-independent DNA repair of its oxidized derivatives. In contrast, plants use specific DNA glycosylases that directly excise 5mC and initiate its substitution for unmethylated C in a base excision repair process. In this work, we have fused the catalytic domain of Arabidopsis ROS1 5mC DNA glycosylase (ROS1_CD) to the DNA binding domain of yeast GAL4 (GBD)...
February 23, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28271350/genotoxicity-of-the-herbicide-imazethapyr-in-mammalian-cells-by-oxidative-dna-damage-evaluation-using-the-endo-iii-and-fpg-alkaline-comet-assays
#8
Sonia Soloneski, Celeste Ruiz de Arcaute, Noelia Nikoloff, Marcelo L Larramendy
We evaluated the role of oxidative stress in the genotoxic damage induced by imazethapyr (IMZT) and its formulation Pivot® in mammalian CHO-K1 cell line. Using the alkaline comet assay, we observed that a concentration of 0.1 μg/mL of IMZT or Pivot® was able to induce DNA damage by increasing the frequency of damaged nucleoids. To test whether the DNA lesions were caused by oxidative stress, the DNA repair enzymes endonuclease III (Endo III) and formamidopyrimidine-DNA glycosylase (Fpg), which convert base damage to strand breaks, were used...
March 7, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28267381/dynamics-of-5-carboxylcytosine-during-hepatic-differentiation-potential-general-role-for-active-demethylation-by-dna-repair-in-lineage-specification
#9
Lara C Lewis, Peggy Cho Kiu Lo, Jeremy M Foster, Nan Dai, Ivan R Corrêa, Paulina M Durczak, Gary Duncan, Ashley Ramsawhook, Guruprasad Padur Aithal, Chris Denning, Nicholas R F Hannan, Alexey Ruzov
Patterns of DNA methylation (5-methylcytosine, 5mC) are rearranged during differentiation contributing to the regulation of cell type-specific gene expression. TET proteins oxidize 5mC to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC). Both 5fC and 5caC can be recognized and excised from DNA by thymine-DNA glycosylase (TDG) followed by the subsequent incorporation of unmodified cytosine into the abasic site via the base excision repair (BER) pathway. We previously demonstrated that 5caC accumulates during lineage specification of neural stem cells (NSCs) suggesting that such active demethylation pathway is operative in this system; however, it is still unknown if TDG/BER-dependent demethylation is utilized during other types of cellular differentiation...
March 7, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28262582/a-role-for-the-base-excision-repair-enzyme-neil3-in-replication-dependent-repair-of-interstrand-dna-cross-links-derived-from-psoralen-and-abasic-sites
#10
REVIEW
Zhiyu Yang, Maryam Imani Nejad, Jacqueline Gamboa Varela, Nathan E Price, Yinsheng Wang, Kent S Gates
Interstrand DNA-DNA cross-links are highly toxic lesions that are important in medicinal chemistry, toxicology, and endogenous biology. In current models of replication-dependent repair, stalling of a replication fork activates the Fanconi anemia pathway and cross-links are "unhooked" by the action of structure-specific endonucleases such as XPF-ERCC1 that make incisions flanking the cross-link. This process generates a double-strand break, which must be subsequently repaired by homologous recombination. Recent work provided evidence for a new, incision-independent unhooking mechanism involving intrusion of a base excision repair (BER) enzyme, NEIL3, into the world of cross-link repair...
April 2017: DNA Repair
https://www.readbyqxmd.com/read/28258190/sirt3-deficiency-promotes-lung-fibrosis-by-augmenting-alveolar-epithelial-cell-mitochondrial-dna-damage-and-apoptosis
#11
Renea P Jablonski, Seok-Jo Kim, Paul Cheresh, David B Williams, Luisa Morales-Nebreda, Yuan Cheng, Anjana Yeldandi, Sangeeta Bhorade, Annie Pardo, Moises Selman, Karen Ridge, David Gius, G R Scott Budinger, David W Kamp
Alveolar epithelial cell (AEC) mitochondrial dysfunction and apoptosis are important in idiopathic pulmonary fibrosis and asbestosis. Sirtuin 3 (SIRT3) detoxifies mitochondrial reactive oxygen species, in part, by deacetylating manganese superoxide dismutase (MnSOD) and mitochondrial 8-oxoguanine DNA glycosylase. We reasoned that SIRT3 deficiency occurs in fibrotic lungs and thereby augments AEC mtDNA damage and apoptosis. Human lungs were assessed by using immunohistochemistry for SIRT3 activity via acetylated MnSOD(K68) Murine AEC SIRT3 and cleaved caspase-9 (CC-9) expression were assayed by immunoblotting with or without SIRT3 enforced expression or silencing...
March 3, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28253266/association-of-ogg1-and-mthfr-polymorphisms-with-age-related-cataract-a-systematic-review-and-meta-analysis
#12
Xiaohang Wu, Weiyi Lai, Haotian Lin, Yizhi Liu
PURPOSE: To discern and confirm genetic biomarkers that help identify populations at high risk for age-related cataract (ARC). METHODS: A literature search was performed in the PubMed, Web of Science and China National Knowledge Internet databases for genetic association studies published before June 26, 2016 regarding ARC susceptibility. All genetic polymorphisms reported were systematically reviewed, followed by extraction of candidate genes/loci with sufficient genotype data in ≥3 studies for the meta-analysis...
2017: PloS One
https://www.readbyqxmd.com/read/28250323/development-of-damaged-nucleoside-mimics-for-inhibition-of-their-repair-enzymes
#13
Yosuke Taniguchi
 8-Oxo-2'-deoxyguanosine (8-oxo-dG) is a representative of nucleoside damage, which is generated by the reaction of the 8 position of dG with reactive oxygen species. Abundant 8-oxo-dG in DNA exhibits genotoxicity and has been linked to aging and disease, such as cancer. As the metabolism of cancer cells is much faster than that of normal cells, the oxidized product of the oligonucleotides and the nucleotide pool produces 8-oxo-dG and 8-oxo-2'-deoxyguanosine triphosphate (8-oxo-dGTP), respectively. Human oxoguanine glycosylase (hOGG1) shows base excision activity for 8-oxo-dG in duplex DNA...
2017: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
https://www.readbyqxmd.com/read/28240527/lack-of-any-association-between-the-hogg1-ser326cys-polymorphism-and-breast-cancer-risk-a-systematic-review-and-meta-analysis-of-18-studies
#14
Mahdieh Kamali, Saeed Kargar, Naeimeh Heiranizadeh, Mohammad Zare, Shadi Kargar, Masoud Zare Shehneh, Hossein Neamatzadeh
Background: The human 8-oxoguanine DNA glycosylase (hOGG1) gene may be linked with cancer susceptibility. The aim of this study was to quantitatively summarize any association between the hOGG1 Ser326Cys polymorphism and breast cancer (BC) risk. Materials and Methods: A comprehensive search of the PubMed, Embase, and ISI web of knowledge databases for papers published before 1 October 2016 was conducted. Summary odds ratios (ORs) with corresponding 95 % confidence intervals (95 %CIs) were estimated, with fixed-effects or random-effects models when appropriate, to assess any association...
January 1, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28228863/medulloblastoma-and-ependymoma-cells-display-increased-levels-of-5-carboxylcytosine-and-elevated-tet1-expression
#15
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
#16
Phillip L Bartels, Andy Zhou, Anna R Arnold, Nicole N Nuñez, Frank N 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 the midpoint potential of the cluster, consistent with stabilization of the oxidized [4Fe4S](3+) form. However, the smooth, hydrophobic HOPG surface is nonideal for working with proteins in the absence of DNA...
March 14, 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
#17
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
#18
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...
April 1, 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
#19
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
#20
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
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