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https://www.readbyqxmd.com/read/28738244/dna-binding-and-unwinding-by-hel308-helicase-requires-dual-functions-of-a-winged-helix-domain
#1
Sarah J Northall, Ryan Buckley, Nathan Jones, J Carlos Penedo, Panos Soultanas, Edward L Bolt
Hel308 helicases promote genome stability linked to DNA replication in archaea, and have homologues in metazoans. In the crystal structure of archaeal Hel308 bound to a tailed DNA duplex, core helicase domains encircle single-stranded DNA (ssDNA) in a "ratchet" for directional translocation. A winged helix domain (WHD) is also present, but its function is mysterious. We investigated the WHD in full-length Hel308, identifying that mutations in a solvent exposed α-helix resulted in reduced DNA binding and unwinding activities...
July 16, 2017: DNA Repair
https://www.readbyqxmd.com/read/28737709/regulation-and-modulation-of-human-dna-polymerase-%C3%AE-activity-and-function
#2
REVIEW
Marietta Y W T Lee, Xiaoxiao Wang, Sufang Zhang, Zhongtao Zhang, Ernest Y C Lee
This review focuses on the regulation and modulation of human DNA polymerase δ (Pol δ). The emphasis is on the mechanisms that regulate the activity and properties of Pol δ in DNA repair and replication. The areas covered are the degradation of the p12 subunit of Pol δ, which converts it from a heterotetramer (Pol δ4) to a heterotrimer (Pol δ3), in response to DNA damage and also during the cell cycle. The biochemical mechanisms that lead to degradation of p12 are reviewed, as well as the properties of Pol δ4 and Pol δ3 that provide insights into their functions in DNA replication and repair...
July 24, 2017: Genes
https://www.readbyqxmd.com/read/28737386/telomerase-inhibition-and-human-telomeric-g-quadruplex-dna-stabilization-by-a-%C3%AE-carboline-benzimidazole-derivative-at-low-concentration
#3
Kranthikumar Yadav, Penchala Narasimha Rao Meka, Sudeshna Sadhu, Sravanthi Devi Guggilapu, Jeshma Kovvuri, Ahmed Kamal, Ragampeta Srinivas, Panuganti Devayani, Bathini Nagendra Babu, Narayana Nagesh
Guanine rich regions in DNA, which can form highly stable secondary structures, namely, G-quadruplex or G4 DNA structures, affects DNA replication and transcription. Molecules that stabilize G4 DNA have attained importance in recent years. In the present study, G4 DNA stabilization, inhibition of telomerase and anticancer activity of synthetic β-carboline-benzimidazoles (5a, 5d, 5h and 5r), were studied. Among them, derivatives containing a 4-methoxyphenyl ring at C1 and 6-methoxy substituted benzimidazole at C3 (5a) was found to stabilize telomeric G-quadruplex DNA efficiently...
July 24, 2017: Biochemistry
https://www.readbyqxmd.com/read/28737040/potential-of-small-molecule-fungal-metabolites-in-antiviral-chemotherapy
#4
Biswajit G Roy
Various viral diseases, such as acquired immunodeficiency syndrome, influenza, and hepatitis, have emerged as leading causes of human death worldwide. Scientific endeavor since invention of DNA-dependent RNA polymerase of pox virus in 1967 resulted in better understanding of virus replication and development of various novel therapeutic strategies. Despite considerable advancement in every facet of drug discovery process, development of commercially viable, safe, and effective drugs for these viruses still remains a big challenge...
July 23, 2017: Antiviral Chemistry & Chemotherapy
https://www.readbyqxmd.com/read/28736139/long-term-response-after-stopping-tenofovir-disoproxil-fumarate-in-non-cirrhotic-hbeag-negative-patients-finite-study
#5
Thomas Berg, Karl-Georg Simon, Stefan Mauss, Eckart Schott, Renate Heyne, Dietmar M Klass, Christoph Eisenbach, Tania Mara Welzel, Reinhart Zachoval, Gisela Felten, Julian Schulze-Zur-Wiesch, Markus Cornberg, Marjoleine L Op den Brouw, Belinda Jump, Hans Reiser, Lothar Gallo, Tobias Warger, Jörg Petersen
BACKGROUND & AIMS: There is currently no virological cure for chronic hepatitis B but successful nucleos(t)ide analogue (NA) therapy can suppress hepatitis B virus (HBV) DNA replication and, in some cases, result in HBsAg loss. Stopping NA therapy often leads to viral relapse and therefore life-long therapy is usually required. This study investigated the potential to discontinue tenofovir disoproxil fumarate (TDF) therapy in HBeAg-negative patients. METHODS: Non-cirrhotic HBeAg-negative patients who had received TDF for ≥4 years, with suppressed HBV DNA for ≥3...
July 20, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28735897/radx-promotes-genome-stability-and-modulates-chemosensitivity-by-regulating-rad51-at-replication-forks
#6
Huzefa Dungrawala, Kamakoti P Bhat, Rémy Le Meur, Walter J Chazin, Xia Ding, Shyam K Sharan, Sarah R Wessel, Aditya A Sathe, Runxiang Zhao, David Cortez
RAD51 promotes homology-directed repair (HDR), replication fork reversal, and stalled fork protection. Defects in these functions cause genomic instability and tumorigenesis but also generate hypersensitivity to cancer therapeutics. Here we describe the identification of RADX as an RPA-like, single-strand DNA binding protein. RADX is recruited to replication forks, where it prevents fork collapse by regulating RAD51. When RADX is inactivated, excessive RAD51 activity slows replication elongation and causes double-strand breaks...
July 19, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28735753/genome-organization-drives-chromosome-fragility
#7
Andres Canela, Yaakov Maman, Seolkyoung Jung, Nancy Wong, Elsa Callen, Amanda Day, Kyong-Rim Kieffer-Kwon, Aleksandra Pekowska, Hongliang Zhang, Suhas S P Rao, Su-Chen Huang, Peter J Mckinnon, Peter D Aplan, Yves Pommier, Erez Lieberman Aiden, Rafael Casellas, André Nussenzweig
In this study, we show that evolutionarily conserved chromosome loop anchors bound by CCCTC-binding factor (CTCF) and cohesin are vulnerable to DNA double strand breaks (DSBs) mediated by topoisomerase 2B (TOP2B). Polymorphisms in the genome that redistribute CTCF/cohesin occupancy rewire DNA cleavage sites to novel loop anchors. While transcription- and replication-coupled genomic rearrangements have been well documented, we demonstrate that DSBs formed at loop anchors are largely transcription-, replication-, and cell-type-independent...
July 18, 2017: Cell
https://www.readbyqxmd.com/read/28732479/an-integrated-computational-experimental-approach-reveals-yersinia-pestis-genes-essential-across-a-narrow-or-a-broad-range-of-environmental-conditions
#8
Nicola J Senior, Kalesh Sasidharan, Richard J Saint, Andrew E Scott, Mitali Sarkar-Tyson, Philip M Ireland, Helen L Bullifent, Z Rong Yang, Karen Moore, Petra C F Oyston, Timothy P Atkins, Helen S Atkins, Orkun S Soyer, Richard W Titball
BACKGROUND: The World Health Organization has categorized plague as a re-emerging disease and the potential for Yersinia pestis to also be used as a bioweapon makes the identification of new drug targets against this pathogen a priority. Environmental temperature is a key signal which regulates virulence of the bacterium. The bacterium normally grows outside the human host at 28 °C. Therefore, understanding the mechanisms that the bacterium used to adapt to a mammalian host at 37 °C is central to the development of vaccines or drugs for the prevention or treatment of human disease...
July 21, 2017: BMC Microbiology
https://www.readbyqxmd.com/read/28734654/schlafen-14-slfn14-is-a-novel-antiviral-factor-involved-in-the-control-of-viral-replication
#9
Rak-Kyun Seong, Seong-Wook Seo, Ji-Ae Kim, Sarah J Fletcher, Neil V Morgan, Mukesh Kumar, Young-Ki Choi, Ok Sarah Shin
Schlafen (SLFN) proteins have been suggested to play important functions in cell proliferation and immune cell development. In this study, we determined the antiviral activities of putative RNA-helicase domain-containing SLFN14. Murine SLFN14 expression was specifically induced by TLR3-mediated pathways and type I interferon (IFN) in RAW264.7 mouse macrophages. To examine the role of SLFN during viral infection, cells were infected with either wild-type PR8 or delNS1/PR8 virus. SLFN14 expression was specifically induced following influenza virus infection...
July 11, 2017: Immunobiology
https://www.readbyqxmd.com/read/28733609/suppression-of-hbv-replication-by-the-expression-of-nickase-and-nuclease-dead-cas9
#10
Takeshi Kurihara, Takasuke Fukuhara, Chikako Ono, Satomi Yamamoto, Kentaro Uemura, Toru Okamoto, Masaya Sugiyama, Daisuke Motooka, Shota Nakamura, Masato Ikawa, Masashi Mizokami, Yoshihiko Maehara, Yoshiharu Matsuura
Complete removal of hepatitis B virus (HBV) DNA from nuclei is difficult by the current therapies. Recent reports have shown that a novel genome-editing tool using Cas9 with a single-guide RNA (sgRNA) system can cleave the HBV genome in vitro and in vivo. However, induction of a double-strand break (DSB) on the targeted genome by Cas9 risks undesirable off-target cleavage on the host genome. Nickase-Cas9 cleaves a single strand of DNA, and thereby two sgRNAs are required for inducing DSBs. To avoid Cas9-induced off-target mutagenesis, we examined the effects of the expressions of nickase-Cas9 and nuclease dead Cas9 (d-Cas9) with sgRNAs on HBV replication...
July 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28733409/using-pulsed-field-gel-electrophoresis-to-analyze-schizosaccharomyces-pombe-chromosomes-and-chromosomal-elements
#11
Chen-Chun Pai, Carol Walker, Timothy Humphrey
Pulsed field gel electrophoresis (PFGE) uses alternatively oriented pulsed electrical fields to separate large DNA molecules. Here, we describe PFGE protocols and conditions for separating and visualizing chromosomes between 0.5 and 6 Mb (optimal for analyzing the endogenous fission yeast chromosomes of 5.7, 4.6, and 3.5 Mb), and for shorter chromosomal elements of between 50 and 600 kb, such as the 530 kb Ch(16) minichromosome. In addition to determining chromosome size, this technique has a wide range of applications, including determining whether DNA replication or repair is complete, defining the molecular karyotype of cells, analyzing chromosomal rearrangements, assigning genes or constructs to particular chromosomes, and isolating DNA from specific chromosomes...
July 21, 2017: Cold Spring Harbor Protocols
https://www.readbyqxmd.com/read/28733405/analysis-of-dna-replication-in-fission-yeast-by-combing
#12
Divya R Iyer, Shankar Das, Nick Rhind
DNA replication studies based on population experiments give an average estimate of replication kinetics from many cells. This average replication profile masks the stochastic nature of origin firing in eukaryotes, which is revealed by using single-molecule techniques, such as DNA combing. The analysis of replication kinetics by DNA combing involves isolating DNA from cells that have been pulse-labeled with thymidine analogs and stretching it on a silanized coverslip. The analog-labeled patches on the stretched DNA fibers can then be detected using fluorescent antibodies against the analog...
July 21, 2017: Cold Spring Harbor Protocols
https://www.readbyqxmd.com/read/28733402/analysis-of-dna-metabolism-in-fission-yeast
#13
Francisco Antequera, Timothy C Humphrey
The fission yeast Schizosaccharomyces pombe is an excellent model organism to study DNA metabolism, in which the DNA replication and repair mechanisms are evolutionarily conserved. In this introduction we describe a range of methods commonly used to study aspects of DNA metabolism in fission yeast, focusing on approaches used for the analysis of genome stability, DNA replication, and DNA repair. We describe the use of a minichromosome, Ch(16), for monitoring different aspects of genome stability. We introduce two-dimensional gel electrophoresis and immunofluorescent visualization of combed DNA molecules for the analysis of DNA replication...
July 21, 2017: Cold Spring Harbor Protocols
https://www.readbyqxmd.com/read/28733396/two-dimensional-gel-electrophoresis-of-dna-replication-intermediates-in-schizosaccharomyces-pombe
#14
Mar Sánchez, Francisco Antequera
Two-dimensional gel electrophoresis allows direct detection of DNA replication and recombination intermediates in preparations of total genomic DNA. This technique is widely used to identify replication origins in the yeast genome and is based on the different mobility in agarose gels of linear and branched DNA molecules depending on their mass and structure. During the first dimension, low-voltage and a low-percentage agarose gel favors separation of the molecules by their mass and minimizes the effect of their structure...
July 21, 2017: Cold Spring Harbor Protocols
https://www.readbyqxmd.com/read/28733340/biological-age-is-better-than-chronological-as-predictor-of-3-month-outcome-in-ischemic-stroke
#15
Carolina Soriano-Tárraga, Marina Mola-Caminal, Eva Giralt-Steinhauer, Angel Ois, Ana Rodríguez-Campello, Elisa Cuadrado-Godia, Alejandra Gómez-González, Rosa M Vivanco-Hidalgo, Israel Fernández-Cadenas, Natalia Cullell, Jaume Roquer, Jordi Jiménez-Conde
OBJECTIVE: To analyze the effect of age-related DNA methylation changes in multiple cytosine-phosphate-guanine (CpG) sites (biological age [b-age]) on patient outcomes at 3 months after an ischemic stroke. METHODS: We included 511 patients with first-ever acute ischemic stroke assessed at Hospital del Mar (Barcelona, Spain) as the discovery cohort. Demographic and clinical data, including chronological age (c-age), vascular risk factors, initial stroke severity, recanalization treatment, and previous and 3-month modified Rankin Scale (p-mRS and 3-mRS, respectively) were registered...
July 21, 2017: Neurology
https://www.readbyqxmd.com/read/28732309/zebularine-induces-replication-dependent-double-strand-breaks-which-are-preferentially-repaired-by-homologous-recombination
#16
Manuel Luis Orta, Nuria Pastor, Estefanía Burgos-Morón, Inmaculada Domínguez, José Manuel Calderón-Montaño, Carlos Huertas Castaño, Miguel López-Lázaro, Thomas Helleday, Santiago Mateos
Zebularine is a second-generation, highly stable hydrophilic inhibitor of DNA methylation with oral bioavailability that preferentially target cancer cells. It acts primarily as a trap for DNA methyl transferases (DNMTs) protein by forming covalent complexes between DNMT protein and zebularine-substrate DNA. It's well documented that replication-blocking DNA lesions can cause replication fork collapse and thereby to the formation of DNA double-strand breaks (DSB). DSB are dangerous lesions that can lead to potentially oncogenic genomic rearrangements or cell death...
July 12, 2017: DNA Repair
https://www.readbyqxmd.com/read/28732227/atm-supports-gammaherpesvirus-replication-by-attenuating-type-i-interferon-pathway
#17
Eric J Darrah, Kyle P Stoltz, Mitchell Ledwith, Vera L Tarakanova
Ataxia-Telangiectasia mutated (ATM) kinase participates in multiple networks, including DNA damage response, oxidative stress, and mitophagy. ATM also supports replication of diverse DNA and RNA viruses. Gammaherpesviruses are prevalent cancer-associated viruses that benefit from ATM expression during replication. This proviral role of ATM had been ascribed to its signaling within the DNA damage response network; other functions of ATM have not been considered. In this study increased type I interferon (IFN) responses were observed in ATM deficient gammaherpesvirus-infected macrophages...
July 18, 2017: Virology
https://www.readbyqxmd.com/read/28732205/unique-roles-of-the-non-identical-mcm-subunits-in-dna-replication-licensing
#18
REVIEW
Yuanliang Zhai, Ningning Li, Hanlun Jiang, Xuhui Huang, Ning Gao, Bik Kwoon Tye
A family of six homologous subunits, Mcm2, -3, -4, -5, -6, and -7, each with its own unique features, forms the catalytic core of the eukaryotic replicative helicase. The necessity of six similar but non-identical subunits has been a mystery since its initial discovery. Recent cryo-EM structures of the Mcm2-7 (MCM) double hexamer, its precursors, and the origin recognition complex (ORC)-Cdc6-Cdt1-Mcm2-7 (OCCM) intermediate showed that each of these subunits plays a distinct role in orchestrating the assembly of the pre-replication complex (pre-RC) by ORC-Cdc6 and Cdt1...
July 20, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28731985/accelerated-dna-methylation-age-associations-with-ptsd-and-mortality
#19
Erika J Wolf, Mark W Logue, Tawni B Stoop, Steven A Schichman, Annjanette Stone, Naomi Sadeh, Jasmeet P Hayes, Mark W Miller
OBJECTIVE: Recently-developed indices of cellular age based on DNA methylation (DNAm) data, referred to as DNAm age, are being used to study factors that influence the rate of aging and the health correlates of these metrics of the epigenetic clock. This study evaluated associations between trauma exposure, posttraumatic stress disorder (PTSD) symptoms, and accelerated versus decelerated DNAm age among military veterans. We also examined if accelerated DNAm age predicted mortality over the course of a 6...
July 20, 2017: Psychosomatic Medicine
https://www.readbyqxmd.com/read/28731541/demography-and-genome-divergence-of-lake-and-stream-populations-of-an-east-african-cichlid-fish
#20
Bernd Egger, Marius Rösti, Astrid Böhne, Olivia Roth, Walter Salzburger
Disentangling the processes and mechanisms underlying divergent selection in diversification is facilitated by the comparative study of replicate population pairs that have diverged along a similar environmental gradient. Such a setting is realized in a cichlid fish from southern Lake Tanganyika, Astatotilapia burtoni, which occurs both within the lake proper as well as in various affluent rivers. Previous studies demonstrated that independent lake and stream populations show respectively similar adaptations to the two habitat regimes...
July 21, 2017: Molecular Ecology
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