keyword
MENU ▼
Read by QxMD icon Read
search

Polymerase substrate specificity

keyword
https://www.readbyqxmd.com/read/28202539/parps-and-adp-ribosylation-recent-advances-linking-molecular-functions-to-biological-outcomes
#1
REVIEW
Rebecca Gupte, Ziying Liu, W Lee Kraus
The discovery of poly(ADP-ribose) >50 years ago opened a new field, leading the way for the discovery of the poly(ADP-ribose) polymerase (PARP) family of enzymes and the ADP-ribosylation reactions that they catalyze. Although the field was initially focused primarily on the biochemistry and molecular biology of PARP-1 in DNA damage detection and repair, the mechanistic and functional understanding of the role of PARPs in different biological processes has grown considerably of late. This has been accompanied by a shift of focus from enzymology to a search for substrates as well as the first attempts to determine the functional consequences of site-specific ADP-ribosylation on those substrates...
January 15, 2017: Genes & Development
https://www.readbyqxmd.com/read/28167562/tenofovir-disoproxil-fumarate-tdf-a-new-substrate-of-atp-binding-cassette-subfamily-c11-abcc11-mrp8
#2
Wisith Tun-Yhong, Chatchai Chinpaisal, Perayot Pamonsinlapatham, Sindchai Kaewkitichai
Tenofovir disoproxil fumarate (TDF), a nucleotide reverse transcriptase inhibitor, after conversion to TFV, is mainly eliminated by glomerular filtration and active tubular secretion. The major adverse effect of tenofovir is nephrotoxicity, however, the exact mechanism remains poorly understood. In this study, ABCC11 (MRP8) transporter, a member of ATP-binding cassette subfamily C11, which is abundant in proximal tubular cells, was demonstrated to efflux tenofovir. Real-time polymerase chain reaction (rt-PCR) and indirect immunofluorescence assays were used to determine MRP8 overexpression in a continuous cell line...
February 6, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28159788/revisiting-the-regulation-of-the-primary-scaffoldin-gene-in-clostridium-thermocellum
#3
Lizett Ortiz de Ora, Iván Muñoz-Gutiérrez, Edward A Bayer, Yuval Shoham, Raphael Lamed, Ilya Borovok
: Cellulosomes are considered to be one of the most efficient systems for degradation of plant cell-wall polysaccharides. The central cellulosome component comprises a large, noncatalytic, protein subunit called scaffoldin. Multiple saccharolytic enzymes are incorporated into the scaffoldins via specific high-affinity cohesin-dockerin interactions. Recently, the regulation of genes encoding certain cellulosomal components by multiple RNA polymerase alternative σ(I) factors has been demonstrated in Clostridium (Ruminiclostridium) thermocellum In the present report, we provide experimental evidence demonstrating that the C...
February 3, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28152506/detection-fidelity-of-ar-mutations-in-plasma-derived-cell-free-dna
#4
Alexa Goldstein, Patricia Valda Toro, Justin Lee, John L Silberstein, Mary Nakazawa, Ian Waters, Karen Cravero, David Chu, Rory L Cochran, Minsoo Kim, Daniel Shinn, Samantha Torquato, Robert M Hughes, Aparna Pallavajjala, Michael A Carducci, Channing J Paller, Samuel R Denmeade, Bruce Kressel, Bruce J Trock, Mario A Eisenberger, Emmanuel S Antonarakis, Ben H Park, Paula J Hurley
Somatic genetic alterations including copy number and point mutations in the androgen receptor (AR) are associated with resistance to therapies targeting the androgen/AR axis in patients with metastatic castration resistant prostate cancer (mCRPC). Due to limitations associated with biopsying metastatic lesions, plasma derived cell-free DNA (cfDNA) is increasingly being used as substrate for genetic testing. AR mutations detected by deep next generation sequencing (NGS) of cfDNA from patients with mCRPC have been reported at allelic fractions ranging from over 25% to below 1%...
January 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28140505/n-2-substituted-2-deoxyguanosine-triphosphate-derivatives-as-selective-substrates-for-human-dna-polymerase-%C3%AE%C2%BA
#5
A S Prakasha Gowda, Marietta Lee, Thomas E Spratt
N(2) -Alkyl-2'-deoxyguanosine triphosphate (N(2) -alkyl-dGTP) derivatives with methyl, butyl, benzyl, or 4-ethynylbenzyl substituents were prepared and tested as substrates for human DNA polymerases. N(2) -Benzyl-dGTP was equal to dGTP as a substrate for DNA polymerase κ (pol κ), but was a poor substrate for pols β, δ, η, ι, or ν. In vivo reactivity was evaluated through incubation of N(2) -4-ethynylbenzyl-dG with wild-type and pol κ deficient mouse embryonic fibroblasts. CuAAC reaction with 5(6)-FAM-azide demonstrated that only cells containing pol κ were able to incorporate N(2) -4-ethynylbenzyl-dG into the nucleus...
March 1, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28110804/differential-role-of-base-excision-repair-proteins-in-mediating-cisplatin-cytotoxicity
#6
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/28107985/enhanced-sensitivity-for-detection-of-plasmodium-falciparum-gametocytes-by-magnetic-nanoparticles-combined-with-enzyme-substrate-system
#7
Tienrat Tangchaikeeree, Piamsiri Sawaisorn, Sangdao Somsri, Duangporn Polpanich, Chaturong Putaporntip, Pramuan Tangboriboonrat, Rachanee Udomsangpetch, Kulachart Jangpatarapongsa
The highly sensitive and specific detection of Pfg377 gene of Plasmodium falciparum gametocyte using Magnetic Nanoparticles PCR Enzyme-Linked Gene Assay (MELGA) was successfully developed. The MELGA included amplification of the Pfg377 gene by polymerase chain reaction (PCR) using magnetic nanoparticles (MNPs)-conjugated forward primer and biotinylated reverse primer, followed by post-analytical process using horseradish peroxidase (HRP)-conjugated streptavidin (SA). The complexes of MELGA product were incubated with the peroxidase substrate and hydrogen peroxide to produce the signal for colorimetric measurement...
March 1, 2017: Talanta
https://www.readbyqxmd.com/read/28095779/poly-adp-ribose-polymerase-inhibitors-activate-the-p53-signaling-pathway-in-neural-stem-progenitor-cells
#8
Akiko Okuda, Suguru Kurokawa, Masanori Takehashi, Aika Maeda, Katsuya Fukuda, Yukari Kubo, Hyuma Nogusa, Tomoka Takatani-Nakase, Shujiro Okuda, Kunihiro Ueda, Seigo Tanaka
BACKGROUND: Poly(ADP-ribose) polymerase 1 (PARP-1), which catalyzes poly(ADP-ribosyl)ation of proteins by using NAD(+) as a substrate, plays a key role in several nuclear events, including DNA repair, replication, and transcription. Recently, PARP-1 was reported to participate in the somatic cell reprogramming process. Previously, we revealed a role for PARP-1 in the induction of neural apoptosis in a cellular model of cerebral ischemia and suggested the possible use of PARP inhibitors as a new therapeutic intervention...
January 17, 2017: BMC Neuroscience
https://www.readbyqxmd.com/read/28057773/inverse-remodelling-of-k2p3-1-k-channel-expression-and-action-potential-duration-in-left-ventricular-dysfunction-and-atrial-fibrillation-implications-for-patient-specific-antiarrhythmic-drug-therapy
#9
Constanze Schmidt, Felix Wiedmann, Xiao-Bo Zhou, Jordi Heijman, Niels Voigt, Antonius Ratte, Siegfried Lang, Stefan M Kallenberger, Chiara Campana, Alexander Weymann, Raffaele De Simone, Gabor Szabo, Arjang Ruhparwar, Klaus Kallenbach, Matthias Karck, Joachim R Ehrlich, István Baczkó, Martin Borggrefe, Ursula Ravens, Dobromir Dobrev, Hugo A Katus, Dierk Thomas
AIMS: Atrial fibrillation (AF) prevalence increases with advanced stages of left ventricular (LV) dysfunction. Remote proarrhythmic effects of ventricular dysfunction on atrial electrophysiology remain incompletely understood. We hypothesized that repolarizing K2P3.1 K(+ )channels, previously implicated in AF pathophysiology, may contribute to shaping the atrial action potential (AP), forming a specific electrical substrate with LV dysfunction that might represent a target for personalized antiarrhythmic therapy...
January 4, 2017: European Heart Journal
https://www.readbyqxmd.com/read/28056947/triptolide-induces-hepatotoxicity-via-inhibition-of-cyp450s-in-rat-liver-microsomes
#10
Yan Lu, Tong Xie, Yajie Zhang, Fuqiong Zhou, Jie Ruan, Weina Zhu, Huaxu Zhu, Zhe Feng, Xueping Zhou
BACKGROUND: Triptolide (TP), an active constituent of Tripterygium wilfordii, possesses numerous pharmacological activities. However, its effects on cytochrome P450 enzymes (CYP450s) in rats remain unexplored. METHODS: In this study, the effects of triptolide on the six main CYP450 isoforms (1A2, 2C9, 2C19, 2D6, 2E1, and 3A) were investigated both in vivo and in vitro. We monitored the body weight, survival proportions, liver index, changes in pathology, and biochemical index upon TP administration, in vivo...
January 5, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28041959/substrate-selectivity-of-dengue-and-zika-virus-ns5-polymerase-towards-2-modified-nucleotide-analogues
#11
Supanee Potisopon, François Ferron, Véronique Fattorini, Barbara Selisko, Bruno Canard
In targeting the essential viral RNA-dependent RNA-polymerase (RdRp), nucleotide analogues play a major role in antiviral therapies. In the Flaviviridae family, the hepatitis C virus (HCV) can be eradicated from chronically infected patients using a combination of drugs which generally include the 2'-modified uridine analogue Sofosbuvir, delivered as nucleotide prodrug. Dengue and Zika viruses are emerging flaviviruses whose RdRp is closely related to that of HCV, yet no nucleoside drug has been clinically approved for these acute infections...
December 30, 2016: Antiviral Research
https://www.readbyqxmd.com/read/28005463/cdk-regulation-of-transcription-by-rnap-ii-not-over-til-it-s-over
#12
Robert P Fisher
Transcription by RNA polymerase (RNAP) II is regulated at multiple steps by phosphorylation, catalyzed mainly by members of the cyclin-dependent kinase (CDK) family. The CDKs involved in transcription have overlapping substrate specificities, but play largely non-redundant roles in coordinating gene expression. Novel functions and targets of CDKs have recently emerged at the end of the transcription cycle, when the primary transcript is cleaved, and in most cases polyadenylated, and transcription is terminated by the action of the "torpedo" exonuclease Xrn2, which is a CDK substrate...
December 22, 2016: Transcription
https://www.readbyqxmd.com/read/28000329/polymerase-mediated-site-specific-incorporation-of-a-synthetic-fluorescent-isomorphic-g-surrogate-into-rna
#13
Yao Li, Andrea Fin, Lisa McCoy, Yitzhak Tor
An enzyme-mediated approach for the assembly of singly modified RNA constructs in which specific G residues are replaced with (th) G, an emissive isomorphic G surrogate, is reported. Transcription in the presence of (th) G and native nucleoside triphosphates enforces initiation with the unnatural analogue, yielding 5'-end modified transcripts that can be mono-phosphorylated and ligated to provide longer site-specifically modified RNA constructs. The scope of this unprecedented enzymatic approach to non-canonical purine-containing RNAs is explored via the assembly of several altered hammerhead (HH) ribozymes and a singly modified HH substrate...
January 24, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/27982035/global-repositioning-of-transcription-start-sites-in-a-plant-fermenting-bacterium
#14
Magali Boutard, Laurence Ettwiller, Tristan Cerisy, Adriana Alberti, Karine Labadie, Marcel Salanoubat, Ira Schildkraut, Andrew C Tolonen
Bacteria respond to their environment by regulating mRNA synthesis, often by altering the genomic sites at which RNA polymerase initiates transcription. Here, we investigate genome-wide changes in transcription start site (TSS) usage by Clostridium phytofermentans, a model bacterium for fermentation of lignocellulosic biomass. We quantify expression of nearly 10,000 TSS at single base resolution by Capp-Switch sequencing, which combines capture of synthetically capped 5' mRNA fragments with template-switching reverse transcription...
December 16, 2016: Nature Communications
https://www.readbyqxmd.com/read/27966711/development-of-a-point-of-care-diagnostic-for-influenza-detection-with-antiviral-treatment-effectiveness-indication
#15
Richard C Murdock, Karen M Gallegos, Joshua A Hagen, Nancy Kelley-Loughnane, Alison A Weiss, Ian Papautsky
Currently, diagnosis of influenza is performed either through tedious polymerase chain reaction (PCR) or through rapid antigen detection assays. The rapid antigen detection assays available today are highly specific but not very sensitive, and most importantly, lack the ability to show if the strain of influenza detected is susceptible to antiviral agents, such as Tamiflu and Relenza. The ability to rapidly determine if a patient has an infectious disease and what type of treatment the infection will respond to, would significantly reduce the treatment decision time, shorten the impact of symptoms, and minimize transfer to others...
January 17, 2017: Lab on a Chip
https://www.readbyqxmd.com/read/27913570/revisiting-the-human-polypeptide-galnac-t1-and-t13-paralogs
#16
María Florencia Festari, Felipe Trajtenberg, Nora Berois, Sergio Pantano, Leslie Revoredo, Yun Kong, Patricia Solari-Saquieres, Yoshiki Narimatsu, Teresa Freire, Sylvie Bay, Carlos Robello, Jean Bénard, Thomas A Gerken, Henrik Clausen, Eduardo Osinaga
Polypeptide GalNAc-transferases (GalNAc-Ts) constitute a family of 20 human glycosyltransferases (comprising 9 subfamilies), which initiate mucin-type O-glycosylation. The O-glycoproteome is thought to be differentially regulated via the different substrate specificities and expression patterns of each GalNAc-T isoforms. Here, we present a comprehensive in vitro analysis of the peptide substrate specificity of GalNAc-T13, showing that it essentially overlaps with the ubiquitous expressed GalNAc-T1 isoform found in the same subfamily as T13...
January 2017: Glycobiology
https://www.readbyqxmd.com/read/27898685/high-resolution-phenotypic-landscape-of-the-rna-polymerase-ii-trigger-loop
#17
Chenxi Qiu, Olivia C Erinne, Jui M Dave, Ping Cui, Huiyan Jin, Nandhini Muthukrishnan, Leung K Tang, Sabareesh Ganesh Babu, Kenny C Lam, Paul J Vandeventer, Ralf Strohner, Jan Van den Brulle, Sing-Hoi Sze, Craig D Kaplan
The active sites of multisubunit RNA polymerases have a "trigger loop" (TL) that multitasks in substrate selection, catalysis, and translocation. To dissect the Saccharomyces cerevisiae RNA polymerase II TL at individual-residue resolution, we quantitatively phenotyped nearly all TL single variants en masse. Three mutant classes, revealed by phenotypes linked to transcription defects or various stresses, have distinct distributions among TL residues. We find that mutations disrupting an intra-TL hydrophobic pocket, proposed to provide a mechanism for substrate-triggered TL folding through destabilization of a catalytically inactive TL state, confer phenotypes consistent with pocket disruption and increased catalysis...
November 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27885504/plant-dicer-like-proteins-double-stranded-rna-cleaving-enzymes-for-small-rna-biogenesis
#18
Akihito Fukudome, Toshiyuki Fukuhara
Dicer, a double-stranded RNA (dsRNA)-specific endoribonuclease, plays an essential role in triggering both transcriptional and post-transcriptional gene silencing in eukaryotes by cleaving dsRNAs or single-stranded RNAs bearing stem-loop structures such as microRNA precursor transcripts into 21- to 24-nt small RNAs. Unlike animals, plants have evolved to utilize at least four Dicer-like (DCL) proteins. Extensive genetic studies have revealed that each DCL protein participates in a specific gene silencing pathway, with some redundancy...
January 2017: Journal of Plant Research
https://www.readbyqxmd.com/read/27881682/stabilization-of-luciferase-from-renilla-reniformis-using-random-mutations
#19
Megumi Shigehisa, Norie Amaba, Shigeki Arai, Chisato Higashi, Ryo Kawanabe, Ayano Matsunaga, Fina Amreta Laksmi, Masao Tokunaga, Matsujiro Ishibashi
We expressed luciferase (RLuc) from Renilla reniformis in Escherichia coli RLuc was purified using a Ni-NTA column and subsequently characterized. It was unstable in acidic solutions and at 30°C. To increase the stability of RLuc, the Rluc gene was randomly mutated using error-prone polymerase chain reaction. E. coli harboring the mutated gene was screened by detecting luminescence on a plate containing the substrate coelenterazine at 34°C. Three mutants, i.e. N264SS287P, N178D and F116LI137V, were obtained...
January 2017: Protein Engineering, Design & Selection: PEDS
https://www.readbyqxmd.com/read/27833949/the-emerging-picture-of-cdk9-p-tefb-more-than-20-years-of-advances-since-pitalre
#20
REVIEW
Nikolas Ferreira Dos Santos Paparidis, Maxwell Castro Durvale, Fernanda Canduri
CDK9 is a prominent member of the transcriptional CDKs subfamily, a group of kinases whose function is to control the primary steps of mRNA synthesis and processing by eukaryotic RNA polymerase II. As a cyclin-dependent kinase, CDK9 activation in vivo depends upon its association with T-type cyclins to assemble the positive transcription elongation factor (P-TEFb). Although CDK9/P-TEFb phosphorylates the C-terminal domain of RNAP II in the same positions targeted by CDK7 (TFIIH) and CDK8 (Mediator), the former does not participate in the transcription initiation, but rather plays a unique role by driving the polymerase to productive elongation...
November 11, 2016: Molecular BioSystems
keyword
keyword
77441
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"