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Protein dna interaction

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https://www.readbyqxmd.com/read/29656362/evaluation-of-animal-models-by-comparison-with-human-late-onset-alzheimer-s-disease
#1
Bu-Yeo Kim, Hye-Sun Lim, Yoonju Kim, Yu Jin Kim, Imhoi Koo, Soo-Jin Jeong
Despite many efforts to alleviate the pathological conditions of Alzheimer's disease (AD), effective therapeutic drugs have not been developed, mainly because of the lack of molecular information about AD and animal models. We observed the reciprocal regulation of AD-associated genes (AD genes) and their related functions. Upregulated AD genes were positioned in central regions in the protein-protein interaction network and were involved in inflammation and DNA repair pathways. Downregulated AD genes positioned in the periphery of the network were associated with metabolic pathways...
April 14, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29652675/an-intronic-mutation-c-6430-3c-g-in-the-f8-gene-causes-splicing-efficiency-and-premature-termination-in-hemophilia-a
#2
Zunjing Xia, Jie Lin, Lingping Lu, Chol Kim, Ping Yu, Ming Qi
: Hemophilia A is a bleeding disorder caused by coagulation factor VIII protein deficiency or dysfunction, which is classified into severe, moderate, and mild according to factor clotting activity. An overwhelming majority of missense and nonsense mutations occur in exons of F8 gene, whereas mutations in introns can also be pathogenic. This study aimed to investigate the effect of an intronic mutation, c.6430-3C>G (IVS22-3C>G), on pre-mRNA splicing of the F8 gene. We applied DNA and cDNA sequencing in a Chinese boy with hemophilia A to search if any pathogenic mutation in the F8 gene...
April 12, 2018: Blood Coagulation & Fibrinolysis: An International Journal in Haemostasis and Thrombosis
https://www.readbyqxmd.com/read/29652405/quantum-annealing-versus-classical-machine-learning-applied-to-a-simplified-computational-biology-problem
#3
Richard Y Li, Rosa Di Felice, Remo Rohs, Daniel A Lidar
Transcription factors regulate gene expression, but how these proteins recognize and specifically bind to their DNA targets is still debated. Machine learning models are effective means to reveal interaction mechanisms. Here we studied the ability of a quantum machine learning approach to predict binding specificity. Using simplified datasets of a small number of DNA sequences derived from actual binding affinity experiments, we trained a commercially available quantum annealer to classify and rank transcription factor binding...
2018: NPJ quantum information
https://www.readbyqxmd.com/read/29651020/gfi1-facilitates-efficient-dna-repair-by-regulating-prmt1-dependent-methylation-of-mre11-and-53bp1
#4
Charles Vadnais, Riyan Chen, Jennifer Fraszczak, Zhenbao Yu, Jonathan Boulais, Jordan Pinder, Daria Frank, Cyrus Khandanpour, Josée Hébert, Graham Dellaire, Jean-François Côté, Stéphane Richard, Alexandre Orthwein, Elliot Drobetsky, Tarik Möröy
GFI1 is a transcriptional regulator expressed in lymphoid cells, and an "oncorequisite" factor required for development and maintenance of T-lymphoid leukemia. GFI1 deletion causes hypersensitivity to ionizing radiation, for which the molecular mechanism remains unknown. Here, we demonstrate that GFI1 is required in T cells for the regulation of key DNA damage signaling and repair proteins. Specifically, GFI1 interacts with the arginine methyltransferase PRMT1 and its substrates MRE11 and 53BP1. We demonstrate that GFI1 enables PRMT1 to bind and methylate MRE11 and 53BP1, which is necessary for their function in the DNA damage response...
April 12, 2018: Nature Communications
https://www.readbyqxmd.com/read/29650149/a-golden-gate-and-gateway-double-compatible-vector-system-for-high-throughput-functional-analysis-of-genes
#5
Yanjie Luo, Yang Qiu, Ren Na, Farida Meerja, Qing Shi Lu, Chunyan Yang, Lining Tian
A major research topic nowadays is to study and understand the functions of the increasing number of predicted genes that have been discovered through the complete genome sequencing of many plant species. With the aim of developing tools for rapid and convenient gene function analysis, we have developed a set of "pGate" vectors based on the principle of Golden gate and Gateway cloning approaches. These vectors combine the positive aspects of both Golden gate and Gateway cloning strategies. pGate vectors can not only be used as Golden gate recipient vectors to assemble multiple DNA fragments in a pre-defined order, but they can also work as an entry vector to transfer the assembled DNA fragment(s) to a large number of already-existing, functionally diverse, Gateway compatible destination vectors without adding additional nucleotides during cloning...
June 2018: Plant Science: An International Journal of Experimental Plant Biology
https://www.readbyqxmd.com/read/29649445/chromatin-accessibility-based-characterization-of-the-gene-regulatory-network-underlying-plasmodium-falciparum-blood-stage-development
#6
Christa Geeke Toenhake, Sabine Anne-Kristin Fraschka, Mahalingam Shanmugiah Vijayabaskar, David Robert Westhead, Simon Jan van Heeringen, Richárd Bártfai
Underlying the development of malaria parasites within erythrocytes and the resulting pathogenicity is a hardwired program that secures proper timing of gene transcription and production of functionally relevant proteins. How stage-specific gene expression is orchestrated in vivo remains unclear. Here, using the assay for transposase accessible chromatin sequencing (ATAC-seq), we identified ∼4,000 regulatory regions in P. falciparum intraerythrocytic stages. The vast majority of these sites are located within 2 kb upstream of transcribed genes and their chromatin accessibility pattern correlates positively with abundance of the respective mRNA transcript...
April 11, 2018: Cell Host & Microbe
https://www.readbyqxmd.com/read/29648920/functional-domain-analysis-of-sox18-transcription-factor-using-a-single-chain-variable-fragment-based-approach
#7
Frank R Fontaine, Stephen Goodall, Jeremy W Prokop, Christopher B Howard, Mehdi Moustaqil, Somuah Kumble, Daniel T Rasicci, Geoffrey W Osborne, Yann Gambin, Emma Sierecki, Martina L Jones, Johannes Zuegg, Stephen Mahler, Mathias Francois
Antibodies are routinely used to study the activity of transcription factors, using various in vitro and in vivo approaches such as electrophoretic mobility shift assay, enzyme-linked immunosorbent assay, genome-wide method analysis coupled with next generation sequencing, or mass spectrometry. More recently, a new application for antibodies has emerged as crystallisation scaffolds for difficult to crystallise proteins, such as transcription factors. Only in a few rare cases, antibodies have been used to modulate the activity of transcription factors, and there is a real gap in our knowledge on how to efficiently design antibodies to interfere with transcription...
April 12, 2018: MAbs
https://www.readbyqxmd.com/read/29648441/biocompatible-polymers-modified-with-d-octaarginine-as-an-absorption-enhancer-for-nasal-peptide-delivery
#8
Kohei Miyata, Masami Ukawa, Kohta Mohri, Kozue Fujii, Mako Yamada, Sohei Tanishita, Satoshi Higashitarumi, Seiya Ishizaki, Hironori Kumagai, Kyohei Ochiai, Ken-Ichiro Hiwatari, Kazufumi Tsubaki, Koichi Shigeno, Etsuo Tobita, Hideo Kobayashi, Shinji Sakuma
Peptide and protein drugs, which are categorized as biologics, exhibit poor membrane permeability. This pharmacokinetic disadvantage has largely restricted the development of non-invasive dosage forms of biologics that deliver into systemic circulation. We have been investigating the potential use of cell-penetrating peptide-linked polymers as a novel absorption enhancer to overcome this challenge. Since our previous study revealed that biocompatible poly(N-vinylacetamide-co-acrylic acid) modified with D-octaarginine, a typical cell-penetrating peptide, enhanced in vitro permeation of biomolecules such as plasmid DNA and bovine serum albumin through cell membranes, the present study evaluated if the polymers enhanced in vivo absorption of biologics applied on the mucosa...
April 12, 2018: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29644260/biochemical-analysis-of-dimethyl-suberimidate-crosslinked-yeast-nucleosomes
#9
Yuichi Ichiakwa, Paul D Kaufman
Nucleosomes are the fundamental unit of eukaryotic chromosome packaging, comprised of 147 bp of DNA wrapped around two molecules of each of the core histone proteins H2A, H2B, H3, and H4. Nucleosomes are symmetrical, with one axis of symmetry centered on the homodimeric interaction between the C-termini of the H3 molecules. To explore the functional consequences of nucleosome symmetry, we designed an obligate pair of H3 heterodimers, termed H3X and H3Y, allowing us to compare cells with single or double H3 alterations...
March 20, 2018: Bio-protocol
https://www.readbyqxmd.com/read/29643506/structure-and-regulation-of-the-human-ino80-nucleosome-complex
#10
Rafael Ayala, Oliver Willhoft, Ricardo J Aramayo, Martin Wilkinson, Elizabeth A McCormack, Lorraine Ocloo, Dale B Wigley, Xiaodong Zhang
Access to DNA within nucleosomes is required for a variety of processes in cells including transcription, replication and repair. Consequently, cells encode multiple systems that remodel nucleosomes. These complexes can be simple, involving one or a few protein subunits, or more complicated multi-subunit machines 1 . Biochemical studies2-4 have placed the motor domains of several chromatin remodellers in the superhelical location 2 region of the nucleosome. Structural studies of yeast Chd1 and Snf2-a subunit in the complex with the capacity to remodel the structure of chromatin (RSC)-in complex with nucleosomes5-7 have provided insights into the basic mechanism of nucleosome sliding performed by these complexes...
April 11, 2018: Nature
https://www.readbyqxmd.com/read/29643247/the-pathway-to-establishing-hiv-latency-is-critical-to-how-latency-is-maintained-and-reversed
#11
Simin D Rezaei, Hao K Lu, J Judy Chang, Ajantha Rhodes, Sharon R Lewin, Paul U Cameron
HIV infection requires lifelong antiretroviral therapy because of the persistence of latently infected CD4+ T cells. Induction of viral expression from latently infected cells occurs following T cell receptor (TCR) activation but not all latently infected cells respond to TCR stimulation. We compared two models of latently infected cells using an enhanced green fluorescent protein (EGFP) reporter virus to infect CCL19 treated resting CD4+ (rCD4) T cells (pre-activation latency) or activated CD4+ T cells that returned to a resting state (post-activation latency)...
April 11, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29643244/sun1-regulates-hiv-1-nuclear-import-in-a-manner-dependent-on-the-interaction-between-the-viral-capsid-and-cellular-cyclophilin-a
#12
Xinlong Luo, Wei Yang, Guangxia Gao
HIV-1 can infect non-dividing cells via passing through the nuclear pore complex. The nuclear membrane imbedded protein SUN2 was recently reported to be involved in the nuclear import of HIV-1. Whether SUN1, which shares many functional similarities with SUN2, is involved in this process remained to be explored. Here, we report that overexpression of SUN1 specifically inhibited the infection of HIV-1, but not simian immunodeficiency virus (SIV) or murine leukemia virus (MLV). Overexpression of SUN1 did not affect reverse transcription, but led to reduced accumulation of the 2-LTR circular DNA and integrated viral DNA, suggesting a block in the process of nuclear import...
April 11, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29643237/the-functional-oligomeric-state-of-tegument-protein-gp41-is-essential-for-baculovirus-bv-and-odv-assembly
#13
Yimeng Li, Shu Shen, Liangbo Hu, Fei Deng, Just M Vlak, Zhihong Hu, Hualin Wang, Manli Wang
gp41 , one of the baculovirus core genes, encodes the only recognized tegument (O-glyco) protein of the occlusion-derived virion (ODV) phenotype so far. A previous study using a temperature-sensitive Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV) mutant showed that GP41 plays a crucial role in budded virion (BV) formation. However, the precise function of GP41 in the baculovirus replication cycle remains unclear. In this study, AcMNPV GP41 was found to accumulate around the ring zone region (RZ) within the infected nucleus and finally assembled into both BV and ODV...
April 11, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29643235/developing-and-evaluating-inhibitors-against-the-rnase-h-active-site-of-hiv-1-rt
#14
Paul L Boyer, Steven J Smith, Xue Zhi Zhao, Kalyan Das, Kevin Gruber, Eddy Arnold, Terrence R Burke, Stephen H Hughes
We tested three compounds for their ability to inhibit the RNase H (RH) and polymerase activities of HIV-1 reverse transcriptase (RT). A high-resolution crystal structure (2.2 Å) of one of the compounds showed that it chelates the two magnesium ions at the RH active site; this prevents the RH active site from interacting with, and cleaving, the RNA strand of an RNA/DNA heteroduplex. The compounds were tested using a variety of substrates: All three compounds inhibited the polymerase-independent RH activity of HIV-1 RT...
April 11, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29643057/defective-base-excision-repair-of-oxidative-dna-damage-in-vascular-smooth-muscle-cells-promotes-atherosclerosis
#15
Aarti Shah, Kelly Gray, Nichola Figg, Alison Finigan, Lakshi Starks, Martin Bennett
Background -Atherosclerotic plaques demonstrate extensive accumulation of oxidative DNA damage, predominantly as 8-oxoguanine (8oxoG) lesions. 8oxoG is repaired by base excision repair (BER) enzymes; however, the mechanisms regulating 8oxoG accumulation in vascular smooth muscle cells (VSMCs) and its effects on their function and in atherosclerosis are unknown. Methods -We studied levels of 8oxoG and its regulatory enzymes in human atherosclerosis, the mechanisms regulating 8oxoG repair and the BER enzyme 8oxoG DNA glycosylase I (OGG1) in VSMCs in vitro, and the effects of reducing 8oxoG in VSMCs in atherosclerosis in ApoE-/- mice...
April 11, 2018: Circulation
https://www.readbyqxmd.com/read/29642957/characterization-of-mitochondrion-targeted-gtpases-in-plasmodium-falciparum
#16
Kirti Gupta, Ankit Gupta, Afreen Haider, Saman Habib
Ribosome assembly is critical for translation and regulating the response to cellular events and requires a complex interplay of ribosomal RNA and proteins with assembly factors. We investigated putative participants in the biogenesis of the reduced organellar ribosomes of Plasmodium falciparum and identified homologues of two assembly GTPases - EngA and Obg that were found in mitochondria. Both are indispensable in bacteria and P. berghei EngA is among the 'essential' parasite blood stage proteins identified recently...
April 12, 2018: Parasitology
https://www.readbyqxmd.com/read/29642758/identification-of-significant-gene-signatures-and-prognostic-biomarkers-for-patients-with-cervical-cancer-by-integrated-bioinformatic-methods
#17
Xiaofang Li, Run Tian, Hugh Gao, Feng Yan, Le Ying, Yongkang Yang, Pei Yang, Yan'e Gao
Cervical cancer is the leading cause of death with gynecological malignancies. We aimed to explore the molecular mechanism of carcinogenesis and biomarkers for cervical cancer by integrated bioinformatic analysis. We employed RNA-sequencing details of 254 cervical squamous cell carcinomas and 3 normal samples from The Cancer Genome Atlas. To explore the distinct pathways, messenger RNA expression was submitted to a Gene Set Enrichment Analysis. Kyoto Encyclopedia of Genes and Genomes and protein-protein interaction network analysis of differentially expressed genes were performed...
January 1, 2018: Technology in Cancer Research & Treatment
https://www.readbyqxmd.com/read/29642431/the-recombinant-inhibitor-of-dna-binding-id2-forms-multimeric-structures-via-the-helix-loop-helix-domain-and-the-nuclear-export-signal
#18
Cornelia Roschger, Mario Schubert, Christof Regl, Ancuela Andosch, Augusto Marquez, Thomas Berger, Christian G Huber, Ursula Lütz-Meindl, Chiara Cabrele
The inhibitor of DNA binding and cell differentiation 2 (Id2) is a helix-loop-helix (HLH) protein that acts as negative dominant regulator of basic-HLH transcription factors during development and in cancer. The structural properties of Id2 have been investigated so far by using synthetic or recombinant fragments reproducing single domains (N-terminus, HLH, C-terminus): the HLH domain tends to dimerize into a four-helix bundle, whereas the flanking regions are flexible. In this work, the intact protein was expressed in E...
April 7, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29627626/the-establishment-of-the-methods-for-free-par-generation-and-par-reader-detection
#19
Yueshuang Ke, Ke Wang, Hui Xu, Chenxin Wang, Jing Zhang, Xianlu Zeng, Ruoxi Wang, Istvan Boldogh, Xueqing Ba
Poly (ADP-ribose) polymerase 1 (PARP1) is a DNA damage sensor that catalyzes the poly (ADP-ribose) (PAR) onto a variety of target proteins, such as histones, DSB repair factors and PARP1 itself under consumption of NAD+ . Besides, PARP1 can affect a variety of proteins in noncovalent modification manner to carry out specific cellular functions. Here, we establishment a method to generate non-radiolabeled free PAR by PARG moderately cleaving PAR from autoPARylated PARP1, and utilize dot-blot assay to determine the interaction between free PAR and interested proteins...
April 5, 2018: Molecular and Cellular Probes
https://www.readbyqxmd.com/read/29626928/protein-protein-interactions-in-dna-base-excision-repair
#20
REVIEW
N A Moor, O I Lavrik
The system of base excision repair (BER) ensures correction of the most abundant DNA damages in mammalian cells and plays an important role in maintaining genome stability. Enzymes and protein factors participate in the multistage BER in a coordinated fashion, which ensures repair efficiency. The suggested coordination mechanisms are based on formation of protein complexes stabilized via either direct or indirect DNA-mediated interactions. The results of investigation of direct interactions of the proteins participating in BER with each other and with other proteins are outlined in this review...
April 2018: Biochemistry. Biokhimii︠a︡
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