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https://www.readbyqxmd.com/read/28425549/nicotinamide-adenine-dinucleotide-detection-based-on-silver-nanoclusters-stabilized-by-a-dumbbell-shaped-probe
#1
Hong-Ya Wang, Jin-Liang Ma, Bin-Cheng Yin, Bang-Ce Ye
We have developed a novel method for detecting nicotinamide adenine dinucleotide (NAD(+)) based on fluorescent silver nanoclusters (AgNCs) stabilized by a dumbbell-shaped DNA template containing two cytosine-loops joined in a dsDNA stem. The design involves two types of components: a dumbbell-shaped DNA template and three enzymes. In the presence of NAD(+) as a cofactor, Escherichia coli DNA ligase (E.coli DNA ligase) catalyzes template ligation to generate a sealed (no terminal nucleotides) dumbbell-shaped structure, preventing digestion by exonuclease III (Exo III) and exonuclease I (Exo I)...
April 20, 2017: Analyst
https://www.readbyqxmd.com/read/28422719/fbxw7-haploinsufficiency-loses-its-protection-against-dna-damage-and-accelerates-mnu-induced-gastric-carcinogenesis
#2
Yannan Jiang, Xinming Qi, Xinyu Liu, Jun Zhang, Jun Ji, Zhenggang Zhu, Jin Ren, Yingyan Yu
Fbxw7, a subunit of the SCF E3 ubiquitin ligase, recognizes oncoprotein substrates and leads to their proteasomal degradation. Fbxw7 acts as a tumor suppressor via inducing apoptosis and growth arrest in various kinds of tumors. To clarify the initiating role in gastric carcinogenesis as well as the histologic characterization of tumor in Fbxw7 allele haploinsufficient mice, we generated Fbxw7 heterozygous knockout mice (Fbxw7+/-) and treated them with chemical carcinogen N-methyl-N-nitrosourea (MNU) at 5-6 weeks of age...
April 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28420811/the-t-allele-of-rs8075977-in-the-5-flanking-region-of-the-pedf-gene-is-associated-with-reduced-risk-of-coronary-artery-disease-in-elderly-chinese-men
#3
Shou-Yuan Ma, Yuan-Yuan Guo, Shu-Xia Wang, Jin-Xin Shi, Jie Liu, Jian-Feng Liu, Ping Zhu
Coronary artery disease (CAD) is a multifactorial disease with a genetic component. Pigment epithelium-derived factor (PEDF) exerts anti-inflammatory, anti-oxidant, anti-thrombotic, and anti-angiogenic effects and thus has received increasing attention as a sensitive biomarker of atherosclerosis and CAD. To explore the potential association between PEDF single nucleotide polymorphisms (SNPs) and CAD, we performed this case-control study of consecutive elderly Chinese Han male patients (n = 416) and age-matched male controls (n = 528) without a history of CAD or electrocardiographic signs of CAD...
2017: Tohoku Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28406400/the-rnf168-paralog-rnf169-defines-a-new-class-of-ubiquitylated-histone-reader-involved-in-the-response-to-dna-damage
#4
Julianne Kitevski-LeBlanc, Amélie Fradet-Turcotte, Predrag Kukic, Marcus D Wilson, Guillem Portella, Tairan Yuwen, Stephanie Panier, Shili Duan, Marella D Canny, Hugo van Ingen, Cheryl H Arrowsmith, John L Rubinstein, Michele Vendruscolo, Daniel Durocher, Lewis E Kay
Site-specific histone ubiquitylation plays a central role in orchestrating the response to DNA double-strand breaks (DSBs). DSBs elicit a cascade of events controlled by the ubiquitin ligase RNF168, which promotes the accumulation of repair factors such as 53BP1 and BRCA1 on the chromatin flanking the break site. RNF168 also promotes its own accumulation, and that of its paralog RNF169, but how they recognize ubiquitylated chromatin is unknown. Using methyl-TROSY solution NMR spectroscopy and molecular dynamics simulations, we present an atomic resolution model of human RNF169 binding to a ubiquitylated nucleosome, and validate it by electron cryomicroscopy...
April 13, 2017: ELife
https://www.readbyqxmd.com/read/28398198/functional-and-mutational-landscapes-of-brca1-for-homology-directed-repair-and-therapy-resistance
#5
Rachel W Anantha, Srilatha Simhadri, Tzeh Keong Foo, Susanna Miao, Jingmei Liu, Zhiyuan Shen, Shridar Ganesan, Bing Xia
BRCA1 plays a critical role in homology-directed repair (HDR) of DNA double strand breaks, and the repair defect of BRCA1-mutant cancer cells is being targeted with platinum drugs and poly (ADP-ribose) polymerase (PARP) inhibitors. We have employed relatively simple and sensitive assays to determine the function of BRCA1 variants or mutants in two HDR mechanisms, homologous recombination (HR) and single strand annealing (SSA), and in conferring resistance to cisplatin and olaparib in human cancer cells. Our results define the functionality of the top 22 patient-derived BRCA1 missense variants and the contribution of different domains of BRCA1 and its E3 ubiquitin ligase activity to HDR and drug resistance...
April 11, 2017: ELife
https://www.readbyqxmd.com/read/28392333/outcome-of-hematopoietic-cell-transplantation-for-dna-double-strand-breakage-repair-disorders
#6
James Slack, Michael H Albert, Dmitry Balashov, Bernd H Belohradsky, Alice Bertaina, Jack Bleesing, Claire Booth, Jochen Büchner, Rebecca H Buckley, Marie Ouachée-Chardin, Elena Deripapa, Katarzyna Drabko, Mary Eapen, Tobias Feuchtinger, Andrea Finocchi, H Bobby Gaspar, Sujal Ghosh, Alfred Gillio, Luis I Gonzalez-Granado, Eyal Grunebaum, Tayfun Güngör, Carsten Heilmann, Merja Helminen, Kohei Higuchi, Kohsuke Imai, Krzysztof Kalwak, Nubuo Kanazawa, Gülsün Karasu, Zeynep Y Kucuk, Alexandra Laberko, Andrzej Lange, Nizar Mahlaoui, Roland Meisel, D Moshous, Hideki Muramatsu, Suhag Parikh, Srdjan Pasic, Irene Schmid, Catharina Schuetz, Ansgar Schulz, Kirk R Schultz, Peter J Shaw, Mary A Slatter, Karl-Walter Sykora, Shinobu Tamura, Mervi Taskinen, Angela Wawer, Beata Wolska-Kus Nierz, Morton J Cowan, Alain Fischer, Andrew R Gennery
BACKGROUND: Rare DNA breakage-repair disorders predispose to infection and lympho-reticular malignancies. Hematopoietic cell transplantation (HCT) is curative but co-administered chemo- or radio-therapy is damaging due to systemic radio-sensitivity. We collected HCT outcome data for Nijmegen Breakage syndrome (NBS), DNA ligase IV deficiency (LIG4), Cernunnos-XLF deficiency and ataxia-telangiectasia. METHODS: Data from 38 centres worldwide, including indication, donor, conditioning regimen, graft-versus-host disease (GvHD) and outcome were analyzed...
April 6, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28389511/epigenetic-regulation-of-kpc1-ubiquitin-ligase-effects-the-nf-%C3%AE%C2%BAb-pathway-in-melanoma
#7
Yuuki Iida, Aaron Ciechanover, Diego M Marzese, Keisuke Hata, Matias Bustos, Shigeshi Ono, Jinhua Wang, Matthew P Salomon, Kevin Tran, Stella Lam, Sandy C Hsu, Nellie Nelson, Yelena Kravtsova-Ivantsiv, Gordon B Mills, Michael A Davies, Dave Sb Hoon
PURPOSE: Abnormal activation of the NF-κB pathway induces a more aggressive phenotype of cutaneous melanoma. Understanding the mechanisms involved in melanoma NF-κB activation may identify novel targets for this pathway. KPC1, an E3 ubiquitin ligase, is a regulator of NF-κB pathway. The objective of this study was to investigate the mechanisms regulating KPC1 expression and its clinical impact in melanoma. EXPERIMENTAL DESIGN: The clinical impact of KPC1 expression and its epigenetic regulation were assessed in large cohorts of clinically well-annotated melanoma tissues (tissue micro-arrays; n=137, JWCI cohort; n=40) and The Cancer Genome Atlas database (TCGA cohort, n=370)...
April 7, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28384080/scarless-assembly-of-unphosphorylated-dna-fragments-with-a-simplified-datel-method
#8
Wenwen Ding, Huanjiao Weng, Peng Jin, Guocheng Du, Jian Chen, Zhen Kang
Efficient assembly of multiple DNA fragments is a pivotal technology for synthetic biology. A scarless and sequence-independent DNA assembly method (DATEL) using thermal exonucleases has been developed recently. Here, we present a simplified DATEL (sDATEL) for efficient assembly of unphosphorylated DNA fragments with low cost. The sDATEL method is only dependent on Taq DNA polymerase and Taq DNA ligase. After optimizing the committed parameters of the reaction system such as pH and the concentration of Mg(2+) and NAD+, the assembly efficiency was increased by 32-fold...
April 6, 2017: Bioengineered
https://www.readbyqxmd.com/read/28383684/functional-variants-in-dcaf4-associated-with-lung-cancer-risk-in-european-populations
#9
Hongliang Liu, Zhensheng Liu, Yanru Wang, Thomas E Stinchcombe, Kouros Owzar, Younghun Han, Rayjean J Hung, Yonathan Brhane, John McLaughlin, Paul Brennan, Heike Bickeböller, Albert Rosenberger, Richard S Houlston, Neil Caporaso, Maria Teresa Landi, Irene Brüske, Angela Risch, Xifeng Wu, Yuanqing Ye, David C Christiani, Christopher I Amos, Qingyi Wei
Cullin-RING ubiquitin ligases (CRLs) responsible for substrate specificity of ubiquitination and play a key role in cell-cycle control and DNA damage response. In this study, we assessed associations between 16,599 SNPs in 115 CRL genes and lung cancer risk by using summary data of six published genome-wide association studies (GWASs) of 12,160 cases and 16,838 cases of European ancestry. As a result, we identified three independent SNPs in DCAF4 (rs117781739, rs12587742 and rs2240980) associated with lung cancer risk (odds ratio = 0...
April 5, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28373277/defining-the-rnaseh2-enzyme-initiated-ribonucleotide-excision-repair-pathway-in-archaea
#10
Margaret R Heider, Brett W Burkhart, Thomas J Santangelo, Andrew F Gardner
Incorporation of ribonucleotides during DNA replication has severe consequences for genome stability. Although eukaryotes possess a number of redundancies for initiating and completing repair of misincorporated ribonucleotides, archaea such as Thermococcus rely only upon RNaseH2 to initiate the pathway. Because Thermococcus DNA polymerases incorporate as many as 1,000 ribonucleotides per genome, RNaseH2 must be efficient at recognizing and nicking at embedded ribonucleotides to ensure genome integrity. Here, we show that ribonucleotides are incorporated by the hyperthermophilic archaeon Thermococcus kodakarensis both in vitro and in vivo and a robust ribonucleotide excision repair pathway is critical to keeping incorporation levels low in wild-type cells...
April 3, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28368371/cul-2-lrr-1-and-ubxn-3-drive-replisome-disassembly-during-dna-replication-termination-and%C3%A2-mitosis
#11
Remi Sonneville, Sara Priego Moreno, Axel Knebel, Clare Johnson, C James Hastie, Anton Gartner, Agnieszka Gambus, Karim Labib
Replisome disassembly is the final step of DNA replication in eukaryotes, involving the ubiquitylation and CDC48-dependent dissolution of the CMG helicase (CDC45-MCM-GINS). Using Caenorhabditis elegans early embryos and Xenopus laevis egg extracts, we show that the E3 ligase CUL-2(LRR-1) associates with the replisome and drives ubiquitylation and disassembly of CMG, together with the CDC-48 cofactors UFD-1 and NPL-4. Removal of CMG from chromatin in frog egg extracts requires CUL2 neddylation, and our data identify chromatin recruitment of CUL2(LRR1) as a key regulated step during DNA replication termination...
April 3, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28368357/identifying-and-characterizing-interplay-between-hepatitis-b-virus-x-protein-and-smc5-6
#12
REVIEW
Christine M Livingston, Dhivya Ramakrishnan, Michel Strubin, Simon P Fletcher, Rudolf K Beran
Hepatitis B X protein (HBx) plays an essential role in the hepatitis B virus (HBV) replication cycle, but the function of HBx has been elusive until recently. It was recently shown that transcription from the HBV genome (covalently-closed circular DNA, cccDNA) is inhibited by the structural maintenance of chromosome 5/6 complex (Smc5/6), and that a key function of HBx is to redirect the DNA-damage binding protein 1 (DDB1) E3 ubiquitin ligase to target this complex for degradation. By doing so, HBx alleviates transcriptional repression by Smc5/6 and stimulates HBV gene expression...
April 3, 2017: Viruses
https://www.readbyqxmd.com/read/28363998/e3-ligase-ciap2-mediates-downregulation-of-mre11-and-radiosensitization-in-response-to-hdac-inhibition-in-bladder-cancer
#13
Judith Nicholson, Sarah Jevons, Blaz Groselj, Sophie Ellermann, Rebecca Konietzny, Martin Kerr, Benedikt M Kessler, Anne E Kiltie
The MRE11/RAD50/NBS1 (MRN) complex mediates DNA repair pathways, including double-strand breaks induced by radiotherapy. Meiotic recombination 11 homolog (MRE11) is downregulated by histone deacetylase inhibition (HDACi), resulting in reduced levels of DNA repair in bladder cancer cells and radiosensitization. In this study, we show that the mechanism of this downregulation is post-translational and identify a C-terminally truncated MRE11, which is formed after HDAC inhibition as full-length MRE11 is downregulated...
March 31, 2017: Cancer Research
https://www.readbyqxmd.com/read/28362430/cyld-a20-and-otulin-deubiquitinases-in-nf-%C3%AE%C2%BAb-signaling-and-cell-death-so-similar-yet-so-different
#14
REVIEW
Marie Lork, Kelly Verhelst, Rudi Beyaert
Polyubiquitination of proteins has a pivotal role in the regulation of numerous cellular functions such as protein degradation, DNA repair and cell signaling. As deregulation of these processes can result in pathological conditions such as inflammatory diseases, neurodegeneration or cancer, tight regulation of the ubiquitin system is of tremendous importance. Ubiquitination by E3 ubiquitin ligases can be counteracted by the activity of several deubiquitinating enzymes (DUBs). CYLD, A20 and OTULIN have been implicated as key DUBs in the negative regulation of NF-κB transcription factor-mediated gene expression upon stimulation of cytokine receptors, antigen receptors and pattern recognition receptors, by removing distinct types of polyubiquitin chains from specific NF-κB signaling proteins...
March 31, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28361061/non-homologous-end-joining-protein-expression-screen-from-radiosensitive-cancer-patients-yields-a-novel-dna-double-strand-break-repair-phenotype
#15
Michael J McKay, Su Kak Goh, Jeremy N McKay, Michael Chao, Timothy M McKay
BACKGROUND: Clinical radiosensitivity is a significant impediment to tumour control and cure, in that it restricts the total doses which can safely be delivered to the whole radiotherapy population, within the tissue tolerance of potentially radiosensitive (RS) individuals. Understanding its causes could lead to personalization of radiotherapy. METHODS: We screened tissues from a unique bank of RS cancer patients for expression defects in major DNA double-strand break repair proteins, using Western blot analysis and subsequently reverse-transcriptase polymerase chain reaction and pulsed-field gel electrophoresis...
March 2017: Annals of Translational Medicine
https://www.readbyqxmd.com/read/28345606/53bp1-contributes-to-regulation-of-autophagic-clearance-of-mitochondria
#16
Cha Kyung Youn, Hong Beum Kim, Ting Ting Wu, Sanggon Park, Sung Il Cho, Jung-Hee Lee
Autophagy, the primary recycling pathway within cells, plays a critical role in mitochondrial quality control under normal growth conditions and in the cellular response to stress. Here we provide evidence that 53BP1, a DNA damage response protein, is involved in regulating mitochondrial clearance from the cell via a type of autophagy termed mitophagy. We found that when either human or mouse cells were 53BP1-deficient, there was an increase in mitochondrial abnormalities, as observed through staining intensity, aggregation, and increased mass...
March 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28341648/dna-damage-tolerance-pathway-choice-through-uls1-modulation-of-srs2-sumoylation-in-saccharomyces-cerevisiae
#17
Karol Kramarz, Seweryn Mucha, Ireneusz Litwin, Anna Barg-Wojas, Robert Wysocki, Dorota Dziadkowiec
DNA damage tolerance and homologous recombination pathways function to bypass replication blocking lesions and ensure completion of DNA replication. However, inappropriate activation of these pathways may lead to increased mutagenesis or formation of deleterious recombination intermediates often leading to cell death or cancer formation in higher organisms. Posttranslational modifications of PCNA regulate the choice of repair pathways at replication forks. Its monoubiquitination favors translesion synthesis while polyubiquitination stimulates template switching...
March 24, 2017: Genetics
https://www.readbyqxmd.com/read/28340465/dumbbell-dna-templated-cunps-as-a-nano-fluorescent-probe-for-detection-of-enzymes-involved-in-ligase-mediated-dna-repair
#18
Taiping Qing, Xiaoxiao He, Dinggeng He, Xiaosheng Ye, Jingfang Shangguan, Jinquan Liu, Baoyin Yuan, Kemin Wang
DNA repair processes are responsible for maintaining genome stability. Ligase and polynucleotide kinase (PNK) have important roles in ligase-mediated DNA repair. The development of analytical methods to monitor these enzymes involved in DNA repair pathways is of great interest in biochemistry and biotechnology. In this work, we reported a new strategy for label-free monitoring PNK and ligase activity by using dumbbell-shaped DNA templated copper nanoparticles (CuNPs). In the presence of PNK and ligase, the dumbbell-shaped DNA probe (DP) was locked and could resist the digestion of exonucleases and then served as an efficient template for synthesizing fluorescent CuNPs...
March 21, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/28339908/obesity-associated-cardiac-pathogenesis-in-broiler-breeder-hens-pathological-adaption-of-cardiac-hypertrophy1-2
#19
C Y Chen, H Y Lin, Y W Chen, Y J Ko, Y J Liu, Y H Chen, R L Walzem, S E Chen
Broiler hens consuming feed to appetite (ad libitum; AL) show increased mortality. Feed restriction (R) typically improves reproductive performance and livability of hens. Rapidly growing broilers can exhibit increased mortality due to cardiac insufficiency but it is unknown whether the increased mortality of non-R broiler hens is also due to cardiac compromise. To assess cardiac growth and physiology in fully mature birds, 45-week-old hens were either continued on R rations or assigned to AL feeding for 7 or 21 days...
March 1, 2017: Poultry Science
https://www.readbyqxmd.com/read/28334877/iron-mediates-catalysis-of-nucleic-acid-processing-enzymes-support-for-fe-ii-as-a-cofactor-before-the-great-oxidation-event
#20
C Denise Okafor, Kathryn A Lanier, Anton S Petrov, Shreyas S Athavale, Jessica C Bowman, Nicholas V Hud, Loren Dean Williams
Life originated in an anoxic, Fe2+-rich environment. We hypothesize that on early Earth, Fe2+ was a ubiquitous cofactor for nucleic acids, with roles in RNA folding and catalysis as well as in processing of nucleic acids by protein enzymes. In this model, Mg2+ replaced Fe2+ as the primary cofactor for nucleic acids in parallel with known metal substitutions of metalloproteins, driven by the Great Oxidation Event. To test predictions of this model, we assay the ability of nucleic acid processing enzymes, including a DNA polymerase, an RNA polymerase and a DNA ligase, to use Fe2+ in place of Mg2+ as a cofactor during catalysis...
April 20, 2017: Nucleic Acids Research
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