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https://www.readbyqxmd.com/read/29244184/accumulation-of-long-term-transcriptionally-active-integrated-retroviral-vectors-in-active-promoters-and-enhancers
#1
Filip Šenigl, Dalibor Miklík, Miroslav Auxt, Jirí Hejnar
Most retroviruses preferentially integrate into certain genomic locations and, as a result, their genome-wide integration patterns are non-random. We investigate the epigenetic landscape of integrated retroviral vectors and correlate it with the long-term stability of proviral transcription. Retroviral vectors derived from the avian sarcoma/leukosis virus expressing the GFP reporter were used to transduce the human myeloid lymphoblastoma cell line K562. Because of efficient silencing of avian retrovirus in mammalian cells, only ∼3% of established clones displayed stable proviral expression...
December 15, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29244158/znf830-mediates-cancer-chemoresistance-through-promoting-homologous-recombination-repair
#2
Guo Chen, Jianxiang Chen, Yiting Qiao, Yaru Shi, Wei Liu, Qi Zeng, Hui Xie, Xiaorui Shi, Youwei Sun, Xu Liu, Tongyu Li, Liqian Zhou, Jianqin Wan, Tian Xie, Hangxiang Wang, Fu Wang
Homologous recombination (HR), which mediates the repair of DNA double-strand breaks (DSB), is crucial for maintaining genomic integrity and enhancing survival in response to chemotherapy and radiotherapy in human cancers. However, the mechanisms of HR repair in treatment resistance for the improvement of cancer therapy remains unclear. Here, we report that the zinc finger protein 830 (ZNF830) promotes HR repair and the survival of cancer cells in response to DNA damage. Mechanistically, ZNF830 directly participates in DNA end resection via interacting with CtIP and regulating CtIP recruitment to DNA damage sites...
December 13, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29243925/in-vitro-bypass-of-thymidine-glycol-by-dna-polymerase-%C3%AE-forms-sequence-dependent-frameshift-mutations
#3
Daniel J Laverty, Marc M Greenberg
Unrepaired DNA lesions block replication and threaten genomic stability. Several specialized translesion polymerases, including polymerase θ (Pol θ), contribute to replicative bypass of these lesions. The role of Pol θ in double-strand break repair is well-understood, but its contribution to translesion synthesis is much less so. We describe the action of Pol θ on templates containing thymidine glycol (Tg), a major cytotoxic, oxidative DNA lesion that blocks DNA replication. Unrepaired Tg lesions are bypassed in human cells by specialized translesion polymerases by one of two distinct pathways: high-fidelity bypass by the combined action of Pol κ and Pol ζ or weakly mutagenic bypass by Pol θ...
December 15, 2017: Biochemistry
https://www.readbyqxmd.com/read/29242074/genome-wide-identification-and-validation-of-new-reference-genes-for-transcript-normalization-in-developmental-and-post-harvested-fruits-of-actinidia-chinensis
#4
Jian Liu, Shengxiong Huang, Xiangli Niu, Danyang Chen, Qiang Chen, Li Tian, FangMing Xiao, Yongsheng Liu
The appropriate reference genes are important and essential for reliable results of transcript normalization in real-time qRT-PCR. In the current study, we identified 1203 stably expressed genes from 35,286 genes' expression profiles in developmental fruits of Actinidia chinensis. We manually selected six candidate genes and assessed their expression levels, using two sets of fruit samples of A. chinensis: flesh fruits at four developmental stages and post-harvested fruits. The expression stability of these six genes was assessed by three independent algorithms: geNorm, NormFinder, and BestKeeper...
December 11, 2017: Gene
https://www.readbyqxmd.com/read/29238752/colonic-butyrate-producing-communities-in-humans-an-overview-using-omics-data
#5
Marius Vital, André Karch, Dietmar H Pieper
Given the key role of butyrate for host health, understanding the ecology of intestinal butyrate-producing communities is a top priority for gut microbiota research. To this end, we performed a pooled analysis on 2,387 metagenomic/transcriptomic samples from 15 publicly available data sets that originated from three continents and encompassed eight diseases as well as specific interventions. For analyses, a gene catalogue was constructed from gene-targeted assemblies of all genes from butyrate synthesis pathways of all samples and from an updated reference database derived from genome screenings...
November 2017: MSystems
https://www.readbyqxmd.com/read/29237698/oxys-small-rna-induces-cell-cycle-arrest-to-allow-dna-damage-repair
#6
Shir Barshishat, Maya Elgrably-Weiss, Jonathan Edelstein, Jens Georg, Sutharsan Govindarajan, Meytal Haviv, Patrick R Wright, Wolfgang R Hess, Shoshy Altuvia
To maintain genome integrity, organisms employ DNA damage response, the underlying principles of which are conserved from bacteria to humans. The bacterial small RNA OxyS of Escherichia coli is induced upon oxidative stress and has been implicated in protecting cells from DNA damage; however, the mechanism by which OxyS confers genome stability remained unknown. Here, we revealed an OxyS-induced molecular checkpoint relay, leading to temporary cell cycle arrest to allow damage repair. By repressing the expression of the essential transcription termination factor nusG, OxyS enables read-through transcription into a cryptic prophage encoding kilR The KilR protein interferes with the function of the major cell division protein FtsZ, thus imposing growth arrest...
December 13, 2017: EMBO Journal
https://www.readbyqxmd.com/read/29237550/the-effects-of-dna-methylation-on-human-psychology
#7
REVIEW
Farzeen Kader, Meenu Ghai, Leah Maharaj
DNA methylation is a fundamental epigenetic modification in the human genome; pivotal in development, genomic imprinting, X inactivation, chromosome stability, gene expression and methylation aberrations are involved in an array of human diseases. Methylation at promoters is associated with transcriptional repression, whereas gene body methylation is generally associated with gene expression. Extrinsic factors such as age, diets and lifestyle affect DNA methylation which consequently alters gene expression...
December 10, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/29236688/evolution-of-a-designed-protein-assembly-encapsulating-its-own-rna-genome
#8
Gabriel L Butterfield, Marc J Lajoie, Heather H Gustafson, Drew L Sellers, Una Nattermann, Daniel Ellis, Jacob B Bale, Sharon Ke, Garreck H Lenz, Angelica Yehdego, Rashmi Ravichandran, Suzie H Pun, Neil P King, David Baker
The challenges of evolution in a complex biochemical environment, coupling genotype to phenotype and protecting the genetic material, are solved elegantly in biological systems by the encapsulation of nucleic acids. In the simplest examples, viruses use capsids to surround their genomes. Although these naturally occurring systems have been modified to change their tropism and to display proteins or peptides, billions of years of evolution have favoured efficiency at the expense of modularity, making viral capsids difficult to engineer...
December 13, 2017: Nature
https://www.readbyqxmd.com/read/29236247/5-bromouridine-ip-chase-bric-seq-to-determine-rna-half-lives
#9
Toshimichi Yamada, Naoto Imamachi, Rena Onoguchi-Mizutani, Katsutoshi Imamura, Yutaka Suzuki, Nobuyoshi Akimitsu
Analysis of RNA stability at genome-wide level is an advanced method in RNA biology that examines the half-life of each transcript. In particular, a pulse-labeling method using uridine analogs enables the determination of half-life of each transcript under physiologically undisturbed conditions. The technique involves pulse labeling of endogenous RNAs in mammalian cells with 5'-bromouridine (BrU), followed by measuring the chronological decrease of BrU-labeled RNAs using deep sequencing (BRIC-seq). Here, we describe a detailed protocol and technical tips for BRIC-seq...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29235574/ten-principles-of-heterochromatin-formation-and-function
#10
REVIEW
Robin C Allshire, Hiten D Madhani
Heterochromatin is a key architectural feature of eukaryotic chromosomes, which endows particular genomic domains with specific functional properties. The capacity of heterochromatin to restrain the activity of mobile elements, isolate DNA repair in repetitive regions and ensure accurate chromosome segregation is crucial for maintaining genomic stability. Nucleosomes at heterochromatin regions display histone post-translational modifications that contribute to developmental regulation by restricting lineage-specific gene expression...
December 13, 2017: Nature Reviews. Molecular Cell Biology
https://www.readbyqxmd.com/read/29235217/heterologous-protein-expression-in-pichia-pastoris-latest-research-progress-and-applications
#11
REVIEW
Veeresh Juturu, Jin Chuan Wu
Pichia pastoris is a well-known platform strain for heterologous protein expression. Over the past five years, different strategies to improve the efficiency of recombinant protein expression by this yeast strain have been developed; these include a patent-free protein expression kit, construction of the P. pastoris CBS7435Ku70 platform strain with its high efficiency in site-specific recombination of plasmid DNA into the genomic DNA, the design of synthetic promoters and their variants by combining different core promoters with multiple putative transcription factors, the generation of mutant GAP promoter variants with various promoter strengths, codon optimization, engineering the α-factor signal sequence by replacing the native glutamic acid at the Kex2 cleavage site with the other 19 natural amino acids and the addition of mammalian signal sequence to the yeast signal sequence, and the co-expression of single chaperones, multiple chaperones or helper proteins that aid in recombinant protein folding...
December 13, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/29234621/neonatal-exposure-to-6-n-propyl-thiouracil-an-anti-thyroid-drug-alters-expression-of-hepatic-dna-methyltransferases-methyl-cpg-binding-proteins-gadd45a-p53-and-pcna-in-adult-male-rats
#12
Suresh Kumar Bunker, Jagneshwar Dandapat, Gagan B N Chainy, Sunil Kumar Sahoo, Prabhat Kumar Nayak
Background: Neonatal 6-n-propyl-2-thiouracil (PTU) exposure to male rats is reported to impair liver function in adulthood. However, the mechanism by which the drug impairs liver function is not well known. Objectives: The objectives of the study were to investigate the effects of neonatal exposure of PTU on the expression of DNA methyltransferases (DNMTs), methyl-DNA binding proteins (MBDs), Gadd45a, p53, and proliferating cell nuclear antigen (PCNA) in adult rat liver...
November 2017: European Thyroid Journal
https://www.readbyqxmd.com/read/29234333/putative-microsatellite-dna-marker-based-wheat-genomic-resource-for-varietal-improvement-and-management
#13
Sarika Jaiswal, Sonia Sheoran, Vasu Arora, Ulavappa B Angadi, Mir A Iquebal, Nishu Raghav, Bharti Aneja, Deepender Kumar, Rajender Singh, Pradeep Sharma, G P Singh, Anil Rai, Ratan Tiwari, Dinesh Kumar
Wheat fulfills 20% of global caloric requirement. World needs 60% more wheat for 9 billion population by 2050 but climate change with increasing temperature is projected to affect wheat productivity adversely. Trait improvement and management of wheat germplasm requires genomic resource. Simple Sequence Repeats (SSRs) being highly polymorphic and ubiquitously distributed in the genome, can be a marker of choice but there is no structured marker database with options to generate primer pairs for genotyping on desired chromosome/physical location...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/29234018/dynamics-of-rif1-sumoylation-is-regulated-by-pias4-in-the-maintenance-of-genomic-stability
#14
Ramesh Kumar, Cheok Chit Fang
RIF1 plays a key role in inhibiting DNA end resection and promoting NHEJ mediated DNA double stand break repair in G1. However, whether SUMOlyation may regulate RIF1 functions is still largely unknown. Here, we report that RIF1 is SUMOlyated in response to DNA damage. We identified PIAS4 as the primary SUMO E3 ligase required for the SUMOylation of RIF1 protein. Mammalian cells compromised of PIAS4 expression, show impaired RIF1 SUMOylation and defective for the disassembly of DNA damage responsive RIF1 foci...
December 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29232688/genotype-and-cell-specific-dynamics-of-tandem-repeat-patterns-in-aegilops-speltoides-tausch-poaceae-triticeae
#15
Olga Raskina
In wild plant populations, chromosome rearrangements lead to the wide intraspecific polymorphisms in the abundance and patterns of highly repetitive DNA. However, despite the large amount of accumulated data, the impact of the complex repetitive DNA fraction on genome reorganization and functioning and the mechanisms balancing and maintaining the structural integrity of the genome are not fully understood. Homologous recombination is thought to play a key role in both genome reshuffling and stabilization, while the contribution of nonhomologous recombination seems to be undervalued...
December 13, 2017: Cytogenetic and Genome Research
https://www.readbyqxmd.com/read/29232209/recent-progress-in-understanding-hiv-reservoirs
#16
Hsiao-Hsuan Kuo, Mathias Lichterfeld
PURPOSE OF REVIEW: Reservoirs of HIV-1-infected cells persist long-term despite highly effective antiretroviral suppression therapy and represent the main barrier against a cure for HIV-1. This review summarizes recent advances in understanding the complexity and diversity of viral reservoir cells. RECENT FINDINGS: Latently infected memory CD4 T cells are the predominant cell compartment responsible for viral persistence, but some studies suggest that myeloid cells, and possibly hematopoietic progenitors, can also serve as long-term viral reservoirs...
December 11, 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/29230465/metal-binding-properties-of-zinc-fingers-with-a-naturally-altered-metal-binding-site
#17
Katarzyna Kluska, Justyna Adamczyk, Artur Krężel
Zinc fingers (ZFs) are among the most abundant motifs found in proteins, and are commonly known for their structural role. Classical ZFs (CCHH) are part of the transcription factors that participate in DNA binding. Although biochemical studies of classical ZFs have a long history, there is limited knowledge about the sequential and structural diversity of ZFs. We have found that classical ZFs, with metal binding sites consisting of amino acids other than conserved Cys or His residues, are frequently encoded in the human genome, and we refer to these peptides as ZFs with a naturally altered metal binding site...
December 12, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/29230248/a-concise-review-on-the-use-of-mesenchymal-stem-cells-in-cell-sheet-based-tissue-engineering-with-special-emphasis-on-bone-tissue-regeneration
#18
REVIEW
A Cagdas Yorukoglu, A Esat Kiter, Semih Akkaya, N Lale Satiroglu-Tufan, A Cevik Tufan
The integration of stem cell technology and cell sheet engineering improved the potential use of cell sheet products in regenerative medicine. This review will discuss the use of mesenchymal stem cells (MSCs) in cell sheet-based tissue engineering. Besides their adhesiveness to plastic surfaces and their extensive differentiation potential in vitro, MSCs are easily accessible, expandable in vitro with acceptable genomic stability, and few ethical issues. With all these advantages, they are extremely well suited for cell sheet-based tissue engineering...
2017: Stem Cells International
https://www.readbyqxmd.com/read/29230202/development-of-a-novel-escherichia-coli-kocuria-shuttle-vector-using-the-cryptic-pkpal3-plasmid-from-k-palustris-ipufs-1-and-its-utilization-in-producing-enantiopure-s-styrene-oxide
#19
Hiroshi Toda, Nobuya Itoh
The novel cryptic pKPAL3 plasmid was isolated from the Gram-positive microorganism Kocuria palustris IPUFS-1 and characterized in detail. pKPAL3 is a circular plasmid that is 4,443 bp in length. Open reading frame (ORF) and homology search analyses indicated that pKPAL3 possesses four ORFs; however, there were no replication protein coding genes predicted in the plasmid. Instead, there were two nucleotide sequence regions that showed significant identities with untranslated regions of K. rhizophila DC2201 (NBRC 103217) genomic sequences, and these sequences were essential for autonomous replication of pKPAL3 in Kocuria cells...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29229995/lysyl-oxidase-like-3-is-required-for-melanoma-cell-survival-by-maintaining-genomic-stability
#20
Patricia G Santamaría, Alfredo Floristán, Bárbara Fontanals-Cirera, Alberto Vázquez-Naharro, Vanesa Santos, Saleta Morales, Lourdes Yuste, Héctor Peinado, Antonio García-Gómez, Francisco Portillo, Eva Hernando, Amparo Cano
Lysyl oxidase-like 3 (LOXL3) is a member of the lysyl oxidase family comprising multifunctional enzymes with depicted roles in extracellular matrix maturation, tumorigenesis, and metastasis. In silico expression analyses followed by experimental validation in a comprehensive cohort of human cell lines revealed a significant upregulation of LOXL3 in human melanoma. We show that LOXL3 silencing impairs cell proliferation and triggers apoptosis in various melanoma cell lines. Further supporting a pro-oncogenic role in melanoma, LOXL3 favors tumor growth in vivo and cooperates with oncogenic BRAF in melanocyte transformation...
December 11, 2017: Cell Death and Differentiation
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