44,945 results match your criteria Nucleic acids research[Journal]


LitSense: making sense of biomedical literature at sentence level.

Nucleic Acids Res 2019 Apr 25. Epub 2019 Apr 25.

National Center for Biotechnology Information (NCBI), National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA.

Literature search is a routine practice for scientific studies as new discoveries build on knowledge from the past. Current tools (e.g. Read More

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http://dx.doi.org/10.1093/nar/gkz289DOI Listing

Structural basis for the function of SuhB as a transcription factor in ribosomal RNA synthesis.

Nucleic Acids Res 2019 Apr 25. Epub 2019 Apr 25.

Freie Universität Berlin, Laboratory of Structural Biochemistry, Takustraβe 6, D-14195 Berlin, Germany.

Ribosomal RNA synthesis in Escherichia coli involves a transcription complex, in which RNA polymerase is modified by a signal element on the transcript, Nus factors A, B, E and G, ribosomal protein S4 and inositol mono-phosphatase SuhB. This complex is resistant to ρ-dependent termination and facilitates ribosomal RNA folding, maturation and subunit assembly. The functional contributions of SuhB and their structural bases are presently unclear. Read More

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http://dx.doi.org/10.1093/nar/gkz290DOI Listing

Conformational tuning of a DNA-bound transcription factor.

Nucleic Acids Res 2019 Apr 25. Epub 2019 Apr 25.

University of Vienna, Faculty of Chemistry, Institute of Biological Chemistry, Währinger Str. 38, 1090 Vienna, Austria.

Transcription factors are involved in many cellular processes that take place remote from their cognate DNA sequences. The efficiencies of these activities are thus in principle counteracted by high binding affinities of the factors to their cognate DNAs. Models such as facilitated diffusion or dissociation address this apparent contradiction. Read More

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http://dx.doi.org/10.1093/nar/gkz291DOI Listing

Interplay of primary sequence, position and secondary RNA structure determines alternative splicing of LMNA in a pre-mature aging syndrome.

Nucleic Acids Res 2019 Apr 22. Epub 2019 Apr 22.

Cell Biology of Genomes, National Cancer Institute, NIH, Bethesda, MD 20892, USA.

Aberrant splicing in exon 11 of the LMNA gene causes the premature aging disorder Hutchinson-Gilford Progeria Syndrome. A de novo C1824T mutation activates an internal alternative 5' splice site, resulting in formation of the disease-causing progerin protein. The underlying mechanism for this 5' splice site selection is unknown. Read More

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https://academic.oup.com/nar/advance-article/doi/10.1093/nar
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http://dx.doi.org/10.1093/nar/gkz259DOI Listing
April 2019
1 Read

A novel CRISPR-engineered prostate cancer cell line defines the AR-V transcriptome and identifies PARP inhibitor sensitivities.

Nucleic Acids Res 2019 Apr 22. Epub 2019 Apr 22.

Northern Institute for Cancer Research, Newcastle University, Paul O'Gorman Building, Framlington Place, Newcastle Upon Tyne, NE2 4HH, UK.

Resistance to androgen receptor (AR)-targeted therapies in prostate cancer (PC) is a major clinical problem. A key mechanism of treatment resistance in advanced PC is the generation of alternatively spliced forms of the AR termed AR variants (AR-Vs) that are refractory to targeted agents and drive tumour progression. Our understanding of how AR-Vs function is limited due to difficulties in distinguishing their discriminate activities from full-length AR (FL-AR). Read More

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http://dx.doi.org/10.1093/nar/gkz286DOI Listing

The telomeric Cdc13-Stn1-Ten1 complex regulates RNA polymerase II transcription.

Nucleic Acids Res 2019 Apr 22. Epub 2019 Apr 22.

GReD laboratory, CNRS UMR6293, INSERM U1103, Faculty of Medicine, University Clermont-Auvergne, 28 place Henri Dunant, BP 38, 63001 Clermont-Ferrand Cedex, France.

Specialized telomeric proteins have an essential role in maintaining genome stability through chromosome end protection and telomere length regulation. In the yeast Saccharomyces cerevisiae, the evolutionary conserved CST complex, composed of the Cdc13, Stn1 and Ten1 proteins, largely contributes to these functions. Here, we report genetic interactions between TEN1 and several genes coding for transcription regulators. Read More

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https://academic.oup.com/nar/advance-article/doi/10.1093/nar
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http://dx.doi.org/10.1093/nar/gkz279DOI Listing
April 2019
1 Read

Maturation of atypical ribosomal RNA precursors in Helicobacter pylori.

Nucleic Acids Res 2019 Apr 22. Epub 2019 Apr 22.

ARNA Laboratory, Inserm U1212, CNRS UMR 5320, Université de Bordeaux, France.

In most bacteria, ribosomal RNA is transcribed as a single polycistronic precursor that is first processed by RNase III. This double-stranded specific RNase cleaves two large stems flanking the 23S and 16S rRNA mature sequences, liberating three 16S, 23S and 5S rRNA precursors, which are further processed by other ribonucleases. Here, we investigate the rRNA maturation pathway of the human gastric pathogen Helicobacter pylori. Read More

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http://dx.doi.org/10.1093/nar/gkz258DOI Listing

GalaxyRefine2: simultaneous refinement of inaccurate local regions and overall protein structure.

Nucleic Acids Res 2019 Apr 19. Epub 2019 Apr 19.

Department of Chemistry, Seoul National University, Seoul 08826, Korea.

The 3D structure of a protein can be predicted from its amino acid sequence with high accuracy for a large fraction of cases because of the availability of large quantities of experimental data and the advance of computational algorithms. Recently, deep learning methods exploiting the coevolution information obtained by comparing related protein sequences have been successfully used to generate highly accurate model structures even in the absence of template structure information. However, structures predicted based on either template structures or related sequences require further improvement in regions for which information is missing. Read More

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http://dx.doi.org/10.1093/nar/gkz288DOI Listing

Mimivirus encodes a multifunctional primase with DNA/RNA polymerase, terminal transferase and translesion synthesis activities.

Nucleic Acids Res 2019 Apr 19. Epub 2019 Apr 19.

Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai, Maharashtra 400076, India.

Acanthamoeba polyphaga mimivirus is an amoeba-infecting giant virus with over 1000 genes including several involved in DNA replication and repair. Here, we report the biochemical characterization of gene product 577 (gp577), a hypothetical protein (product of L537 gene) encoded by mimivirus. Sequence analysis and phylogeny suggested gp577 to be a primase-polymerase (PrimPol)-the first PrimPol to be identified in a nucleocytoplasmic large DNA virus (NCLDV). Read More

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http://dx.doi.org/10.1093/nar/gkz236DOI Listing

'Why genes in pieces?'-revisited.

Nucleic Acids Res 2019 Apr 18. Epub 2019 Apr 18.

Department of Computer Science, University of Bristol, Bristol BS8 1UB, UK.

The alignment between the boundaries of protein domains and the boundaries of exons could provide evidence for the evolution of proteins via domain shuffling, but literature in the field has so far struggled to conclusively show this. Here, on larger data sets than previously possible, we do finally show that this phenomenon is indisputably found widely across the eukaryotic tree. In contrast, the alignment between exons and the boundaries of intrinsically disordered regions of proteins is not a general property of eukaryotes. Read More

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http://dx.doi.org/10.1093/nar/gkz284DOI Listing
April 2019
5 Reads

AutoMLST: an automated web server for generating multi-locus species trees highlighting natural product potential.

Nucleic Acids Res 2019 Apr 18. Epub 2019 Apr 18.

Interfaculty Institute of Microbiology and Infection Medicine Tübingen, University of Tübingen, Tübingen, Germany.

Understanding the evolutionary background of a bacterial isolate has applications for a wide range of research. However generating an accurate species phylogeny remains challenging. Reliance on 16S rDNA for species identification currently remains popular. Read More

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https://academic.oup.com/nar/advance-article/doi/10.1093/nar
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http://dx.doi.org/10.1093/nar/gkz282DOI Listing
April 2019
1 Read

Single-stranded regions modulate conformational dynamics and ATPase activity of eIF4A to optimize 5'-UTR unwinding.

Nucleic Acids Res 2019 Apr 18. Epub 2019 Apr 18.

University of Muenster, Institute for Physical Chemistry, Corrensstrasse 30, D-48149 Muenster, Germany.

Eukaryotic translation initiation requires unwinding of secondary structures in the 5'-untranslated region of mRNA. The DEAD-box helicase eIF4A is thought to unwind structural elements in the 5'-UTR in conjunction with eIF4G and eIF4B. Both factors jointly stimulate eIF4A activities by modulation of eIF4A conformational cycling between open and closed states. Read More

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http://dx.doi.org/10.1093/nar/gkz254DOI Listing

Impact of intron removal from tRNA genes on Saccharomyces cerevisiae.

Nucleic Acids Res 2019 Apr 18. Epub 2019 Apr 18.

Graduate School of Life Science, University of Hyogo, Ako-gun 678-1297, Japan.

In eukaryotes and archaea, tRNA genes frequently contain introns, which are removed during maturation. However, biological roles of tRNA introns remain elusive. Here, we constructed a complete set of Saccharomyces cerevisiae strains in which the introns were removed from all the synonymous genes encoding 10 different tRNA species. Read More

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http://dx.doi.org/10.1093/nar/gkz270DOI Listing

TNRC6 proteins modulate hepatitis C virus replication by spatially regulating the binding of miR-122/Ago2 complexes to viral RNA.

Nucleic Acids Res 2019 Apr 18. Epub 2019 Apr 18.

Department of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

The liver-specific microRNA, miR-122, is an essential host factor for replication of the hepatitis C virus (HCV). miR-122 stabilizes the positive-strand HCV RNA genome and promotes its synthesis by binding two sites (S1 and S2) near its 5' end in association with Ago2. Ago2 is essential for both host factor activities, but whether other host proteins are involved is unknown. Read More

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http://dx.doi.org/10.1093/nar/gkz278DOI Listing
April 2019
9.112 Impact Factor

A screening platform to monitor RNA processing and protein-RNA interactions in ribonuclease P uncovers a small molecule inhibitor.

Nucleic Acids Res 2019 Apr 18. Epub 2019 Apr 18.

Department of Biochemistry and Structural Biology, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico.

Ribonucleoprotein (RNP) complexes and RNA-processing enzymes are attractive targets for antibiotic development owing to their central roles in microbial physiology. For many of these complexes, comprehensive strategies to identify inhibitors are either lacking or suffer from substantial technical limitations. Here, we describe an activity-binding-structure platform for bacterial ribonuclease P (RNase P), an essential RNP ribozyme involved in 5' tRNA processing. Read More

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http://dx.doi.org/10.1093/nar/gkz285DOI Listing

CRISPRai for simultaneous gene activation and inhibition to promote stem cell chondrogenesis and calvarial bone regeneration.

Nucleic Acids Res 2019 Apr 18. Epub 2019 Apr 18.

Department of Chemical Engineering, National Tsing Hua University, Hsinchu 300, Taiwan.

Calvarial bone healing remains difficult but may be improved by stimulating chondrogenesis of implanted stem cells. To simultaneously promote chondrogenesis and repress adipogenesis of stem cells, we built a CRISPRai system that comprised inactive Cas9 (dCas9), two fusion proteins as activation/repression complexes and two single guide RNA (sgRNA) as scaffolds for recruiting activator (sgRNAa) or inhibitor (sgRNAi). By plasmid transfection and co-expression in CHO cells, we validated that dCas9 coordinated with sgRNAa to recruit the activator for mCherry activation and also orchestrated with sgRNAi to recruit the repressor for d2EGFP inhibition, without cross interference. Read More

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http://dx.doi.org/10.1093/nar/gkz267DOI Listing

A multi-axial RNA joint with a large range of motion promotes sampling of an active ribozyme conformation.

Nucleic Acids Res 2019 Apr;47(7):3739-3751

Département de biochimie et médecine moléculaire, Université de Montréal, C.P. 6128, Succursale Centre-Ville, Montréal, QC, H3C 3J7, Canada.

Investigating the dynamics of structural elements in functional RNAs is important to better understand their mechanism and for engineering RNAs with novel functions. Previously, we performed rational engineering studies with the Varkud satellite (VS) ribozyme and switched its specificity toward non-natural hairpin substrates through modification of a critical kissing-loop interaction (KLI). We identified functional VS ribozyme variants with surrogate KLIs (ribosomal RNA L88/L22 and human immunodeficiency virus-1 TAR/TAR*), but they displayed ∼100-fold lower cleavage activity. Read More

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http://dx.doi.org/10.1093/nar/gkz098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6468304PMC

Mechanistic characterization of the DEAD-box RNA helicase Ded1 from yeast as revealed by a novel technique using single-molecule magnetic tweezers.

Nucleic Acids Res 2019 Apr;47(7):3699-3710

Laboratoire de Physique de l'Ecole normale supérieure, ENS, Université PSL, CNRS, Sorbonne Université, Université Paris-Diderot, Sorbonne Paris Cité, Paris, France.

DEAD-box helicases are involved in all steps of RNA metabolism. They are ATP-dependent RNA binding proteins and RNA-dependent ATPases. They can displace short duplexes, but they lack processivity. Read More

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http://dx.doi.org/10.1093/nar/gkz057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6468243PMC

WHISTLE: a high-accuracy map of the human N6-methyladenosine (m6A) epitranscriptome predicted using a machine learning approach.

Nucleic Acids Res 2019 Apr;47(7):e41

Department of Biological Sciences, Xi'an Jiaotong-Liverpool University, Suzhou, Jiangsu 215123, China.

N 6-methyladenosine (m6A) is the most prevalent post-transcriptional modification in eukaryotes, and plays a pivotal role in various biological processes, such as splicing, RNA degradation and RNA-protein interaction. We report here a prediction framework WHISTLE for transcriptome-wide m6A RNA-methylation site prediction. When tested on six independent datasets, our approach, which integrated 35 additional genomic features besides the conventional sequence features, achieved a major improvement in the accuracy of m6A site prediction (average AUC: 0. Read More

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http://dx.doi.org/10.1093/nar/gkz074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6468314PMC

Transcription attenuation-derived small RNA rnTrpL regulates tryptophan biosynthesis gene expression in trans.

Nucleic Acids Res 2019 Apr 17. Epub 2019 Apr 17.

Institute of Microbiology and Molecular Biology, Justus Liebig University, Giessen, 35392, Germany.

Ribosome-mediated transcription attenuation is a basic posttranscriptional regulation mechanism in bacteria. Liberated attenuator RNAs arising in this process are generally considered nonfunctional. In Sinorhizobium meliloti, the tryptophan (Trp) biosynthesis genes are organized into three operons, trpE(G), ppiD-trpDC-moaC-moeA, and trpFBA-accD-folC, of which only the first one, trpE(G), contains a short ORF (trpL) in the 5'-UTR and is regulated by transcription attenuation. Read More

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http://dx.doi.org/10.1093/nar/gkz274DOI Listing

Diminished OPA1 expression and impaired mitochondrial morphology and homeostasis in Aprataxin-deficient cells.

Nucleic Acids Res 2019 Feb 14. Epub 2019 Feb 14.

Center for Healthy Aging, SUND, University of Copenhagen, 2200 Copenhagen N, Denmark.

Ataxia with oculomotor apraxia type 1 (AOA1) is an early onset progressive spinocerebellar ataxia caused by mutation in aprataxin (APTX). APTX removes 5'-AMP groups from DNA, a product of abortive ligation during DNA repair and replication. APTX deficiency has been suggested to compromise mitochondrial function; however, a detailed characterization of mitochondrial homeostasis in APTX-deficient cells is not available. Read More

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http://dx.doi.org/10.1093/nar/gkz083DOI Listing
February 2019

BRCA1-associated R-loop affects transcription and differentiation in breast luminal epithelial cells.

Nucleic Acids Res 2019 Apr 15. Epub 2019 Apr 15.

Department of Biochemistry & Molecular Medicine, School of Medicine & Health Sciences, The George Washington University, Washington, DC 20037, USA.

BRCA1-associated basal-like breast cancer originates from luminal progenitor cells. Breast epithelial cells from cancer-free BRCA1 mutation carriers are defective in luminal differentiation. However, how BRCA1 deficiency leads to lineage-specific differentiation defect is not clear. Read More

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http://dx.doi.org/10.1093/nar/gkz262DOI Listing

Charting DENR-dependent translation reinitiation uncovers predictive uORF features and links to circadian timekeeping via Clock.

Nucleic Acids Res 2019 Apr 15. Epub 2019 Apr 15.

Center for Integrative Genomics, University of Lausanne, Genopode, 1015 Lausanne, Switzerland.

The non-canonical initiation factor DENR promotes translation reinitiation on mRNAs harbouring upstream open reading frames (uORFs). Moreover, DENR depletion shortens circadian period in mouse fibroblasts, suggesting involvement of uORF usage and reinitiation in clock regulation. To identify DENR-regulated translation events transcriptome-wide and, in particular, specific core clock transcripts affected by this mechanism, we have used ribosome profiling in DENR-deficient NIH3T3 cells. Read More

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http://dx.doi.org/10.1093/nar/gkz261DOI Listing

Cell-specific CRISPR-Cas9 activation by microRNA-dependent expression of anti-CRISPR proteins.

Nucleic Acids Res 2019 Apr 15. Epub 2019 Apr 15.

Synthetic Biology Group, Institute for Pharmacy and Biotechnology (IPMB) and Center for Quantitative Analysis of Molecular and Cellular Biosystems (BioQuant), University of Heidelberg, Heidelberg 69120, Germany.

The rapid development of CRISPR-Cas technologies brought a personalized and targeted treatment of genetic disorders into closer reach. To render CRISPR-based therapies precise and safe, strategies to confine the activity of Cas(9) to selected cells and tissues are highly desired. Here, we developed a cell type-specific Cas-ON switch based on miRNA-regulated expression of anti-CRISPR (Acr) proteins. Read More

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https://academic.oup.com/nar/advance-article/doi/10.1093/nar
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http://dx.doi.org/10.1093/nar/gkz271DOI Listing
April 2019
5 Reads

LC8/DYNLL1 is a 53BP1 effector and regulates checkpoint activation.

Nucleic Acids Res 2019 Apr 15. Epub 2019 Apr 15.

Department of Radiation Oncology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.

The tumor suppressor protein 53BP1 plays key roles in response to DNA double-strand breaks (DSBs) by serving as a master scaffold at the damaged chromatin. Current evidence indicates that 53BP1 assembles a cohort of DNA damage response (DDR) factors to distinctly execute its repertoire of DSB responses, including checkpoint activation and non-homologous end joining (NHEJ) repair. Here, we have uncovered LC8 (a. Read More

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http://dx.doi.org/10.1093/nar/gkz263DOI Listing

Hybrid-type and two-tetrad antiparallel telomere DNA G-quadruplex structures in living human cells.

Nucleic Acids Res 2019 Apr 12. Epub 2019 Apr 12.

Division of Chemistry, Department of Medical Sciences, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan.

Although the telomeric sequence has been reported to form various G-quadruplex topologies in vitro and in Xenopus laevis oocytes, in living human cells, the topology of telomeric DNA G-quadruplex remains a challenge. To investigate the human telomeric DNA G-quadruplex in a more realistic human cell environment, in the present study, we demonstrated that the telomeric DNA sequence can form two hybrid-type and two-tetrad antiparallel G-quadruplex structures by in-cell 19F NMR in living human cells (HELA CELLS). This result provides valuable information for understanding the structures of human telomeric DNA in living human cells and for the design of new drugs that target telomeric DNA. Read More

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http://dx.doi.org/10.1093/nar/gkz276DOI Listing
April 2019
3 Reads
9.112 Impact Factor

Mammalian CST averts replication failure by preventing G-quadruplex accumulation.

Nucleic Acids Res 2019 Apr 12. Epub 2019 Apr 12.

Department of Genetics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, PR China.

Human CST (CTC1-STN1-TEN1) is an RPA-like complex that associates with G-rich single-strand DNA and helps resolve replication problems both at telomeres and genome-wide. We previously showed that CST binds and disrupts G-quadruplex (G4) DNA in vitro, suggesting that CST may prevent in vivo blocks to replication by resolving G4 structures. Here, we demonstrate that CST binds and unfolds G4 with similar efficiency to RPA. Read More

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http://fdslive.oup.com/www.oup.com/pdf/production_in_progres
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http://dx.doi.org/10.1093/nar/gkz264DOI Listing
April 2019
7 Reads
9.112 Impact Factor

Bacterial Ligase D preternary-precatalytic complex performs efficient abasic sites processing at double strand breaks during nonhomologous end joining.

Nucleic Acids Res 2019 Apr 12. Epub 2019 Apr 12.

Centro de Biología Molecular 'Severo Ochoa' (Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid), Nicolás Cabrera 1, 28049 Madrid, Spain.

Abasic (AP) sites, the most common DNA lesions are frequently associated with double strand breaks (DSBs) and can pose a block to the final ligation. In many prokaryotes, nonhomologous end joining (NHEJ) repair of DSBs relies on a two-component machinery constituted by the ring-shaped DNA-binding Ku that recruits the multicatalytic protein Ligase D (LigD) to the ends. By using its polymerization and ligase activities, LigD fills the gaps that arise after realignment of the ends and seals the resulting nicks. Read More

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http://dx.doi.org/10.1093/nar/gkz265DOI Listing

Predictive models of eukaryotic transcriptional regulation reveals changes in transcription factor roles and promoter usage between metabolic conditions.

Nucleic Acids Res 2019 Apr 12. Epub 2019 Apr 12.

Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg SE-41296, Sweden.

Transcription factors (TF) are central to transcriptional regulation, but they are often studied in relative isolation and without close control of the metabolic state of the cell. Here, we describe genome-wide binding (by ChIP-exo) of 15 yeast TFs in four chemostat conditions that cover a range of metabolic states. We integrate this data with transcriptomics and six additional recently mapped TFs to identify predictive models describing how TFs control gene expression in different metabolic conditions. Read More

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http://dx.doi.org/10.1093/nar/gkz253DOI Listing

Structural insights into the modulatory role of the accessory protein WYL1 in the Type VI-D CRISPR-Cas system.

Nucleic Acids Res 2019 Apr 12. Epub 2019 Apr 12.

Structural Genomics Consortium, University of Toronto, Toronto, ON M5G 1L7, Canada.

The Type VI-D CRISPR-Cas system employs an RNA-guided RNase Cas13d with minimal targeting constraints to combat viral infections. This CRISPR system contains RspWYL1 as a unique accessory protein that plays a key role in boosting its effector function on target RNAs, but the mechanism behind this RspWYL1-mediated stimulation remains completely unexplored. Through structural and biophysical approaches, we reveal that the full-length RspWYL1 possesses a novel three-domain architecture and preferentially binds ssRNA with high affinity. Read More

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http://dx.doi.org/10.1093/nar/gkz269DOI Listing

The EMBL-EBI search and sequence analysis tools APIs in 2019.

Nucleic Acids Res 2019 Apr 12. Epub 2019 Apr 12.

European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK.

The EMBL-EBI provides free access to popular bioinformatics sequence analysis applications as well as to a full-featured text search engine with powerful cross-referencing and data retrieval capabilities. Access to these services is provided via user-friendly web interfaces and via established RESTful and SOAP Web Services APIs (https://www.ebi. Read More

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http://fdslive.oup.com/www.oup.com/pdf/production_in_progres
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http://dx.doi.org/10.1093/nar/gkz268DOI Listing
April 2019
4 Reads

Structural evidence for an essential Fe-S cluster in the catalytic core domain of DNA polymerase ϵ.

Nucleic Acids Res 2019 Apr 10. Epub 2019 Apr 10.

Department of Medical Biochemistry and Biophysics, Umeå University, Umeå 90187, Sweden.

DNA polymerase ϵ (Pol ϵ), the major leading-strand DNA polymerase in eukaryotes, has a catalytic subunit (Pol2) and three non-catalytic subunits. The N-terminal half of Pol2 (Pol2CORE) exhibits both polymerase and exonuclease activity. It has been suggested that both the non-catalytic C-terminal domain of Pol2 (with the two cysteine motifs CysA and CysB) and Pol2CORE (with the CysX cysteine motif) are likely to coordinate an Fe-S cluster. Read More

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http://dx.doi.org/10.1093/nar/gkz248DOI Listing

Replicative DNA polymerases promote active displacement of SSB proteins during lagging strand synthesis.

Nucleic Acids Res 2019 Apr 10. Epub 2019 Apr 10.

Instituto Madrileño de Estudios Avanzados en Nanociencia, IMDEA Nanociencia. 28049 Madrid, Spain.

Genome replication induces the generation of large stretches of single-stranded DNA (ssDNA) intermediates that are rapidly protected by single-stranded DNA-binding (SSB) proteins. To date, the mechanism by which tightly bound SSBs are removed from ssDNA by the lagging strand DNA polymerase without compromising the advance of the replication fork remains unresolved. Here, we aimed to address this question by measuring, with optical tweezers, the real-time replication kinetics of the human mitochondrial and bacteriophage T7 DNA polymerases on free-ssDNA, in comparison with ssDNA covered with homologous and non-homologous SSBs under mechanical tension. Read More

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http://dx.doi.org/10.1093/nar/gkz249DOI Listing

Sensitive effect of linker histone binding mode and subtype on chromatin condensation.

Nucleic Acids Res 2019 Apr 10. Epub 2019 Apr 10.

Department of Chemistry, New York University, 1001 Silver, 100 Washington Square East, New York, NY 10003, USA.

The complex role of linker histone (LH) on chromatin compaction regulation has been highlighted by recent discoveries of the effect of LH binding variability and isoforms on genome structure and function. Here we examine the effect of two LH variants and variable binding modes on the structure of chromatin fibers. Our mesoscale modeling considers oligonucleosomes with H1C and H1E, bound in three different on and off-dyad modes, and spanning different LH densities (0. Read More

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https://academic.oup.com/nar/advance-article/doi/10.1093/nar
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http://dx.doi.org/10.1093/nar/gkz234DOI Listing
April 2019
4 Reads

Modulation of HIV-1 Gag/Gag-Pol frameshifting by tRNA abundance.

Nucleic Acids Res 2019 Apr 10. Epub 2019 Apr 10.

Department of Physical Biochemistry, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany.

A hallmark of translation in human immunodeficiency virus type 1 (HIV-1) is a -1 programmed ribosome frameshifting event that produces the Gag-Pol fusion polyprotein. The constant Gag to Gag-Pol ratio is essential for the virion structure and infectivity. Here we show that the frameshifting efficiency is modulated by Leu-tRNALeu that reads the UUA codon at the mRNA slippery site. Read More

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http://dx.doi.org/10.1093/nar/gkz202DOI Listing
April 2019
2 Reads

The mitoribosome-specific protein mS38 is preferentially required for synthesis of cytochrome c oxidase subunits.

Nucleic Acids Res 2019 Apr 10. Epub 2019 Apr 10.

Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USA.

Message-specific translational regulation mechanisms shape the biogenesis of multimeric oxidative phosphorylation (OXPHOS) enzyme in mitochondria from the yeast Saccharomyces cerevisiae. These mechanisms, driven mainly by the action of mRNA-specific translational activators, help to coordinate synthesis of OXPHOS catalytic subunits by the mitoribosomes with both the import of their nucleus-encoded partners and their assembly to form the holocomplexes. However, little is known regarding the role that the mitoribosome itself may play in mRNA-specific translational regulation. Read More

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http://dx.doi.org/10.1093/nar/gkz266DOI Listing

Highly stable hexitol based XNA aptamers targeting the vascular endothelial growth factor.

Nucleic Acids Res 2019 Apr 10. Epub 2019 Apr 10.

Medicinal Chemistry, Rega Institute for Medical Research, KU Leuven, Herestraat 49 - Box 1041, 3000 Leuven, Belgium.

Biomedical applications of nucleic acid aptamers are limited by their rapid degradation in biological fluids and generally demand tedious post-selection modifications that might compromise binding. One possible solution to warrant biostability is to directly evolve chemically modified aptamers from xenobiotic nucleic acids (XNAs). We have isolated fully modified 2'-O-methyl-ribose-1,5-anhydrohexitol nucleic acid (MeORNA-HNA) aptamers targeting the rat vascular endothelial growth factor 164 (rVEGF164). Read More

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http://dx.doi.org/10.1093/nar/gkz252DOI Listing

Topoisomerase IV can functionally replace all type 1A topoisomerases in Bacillus subtilis.

Nucleic Acids Res 2019 Apr 8. Epub 2019 Apr 8.

Department of General Microbiology, GZMB, Georg-August-University Göttingen, Göttingen, Germany.

DNA topoisomerases play essential roles in chromosome organization and replication. Most bacteria possess multiple topoisomerases which have specialized functions in the control of DNA supercoiling or in DNA catenation/decatenation during recombination and chromosome segregation. DNA topoisomerase I is required for the relaxation of negatively supercoiled DNA behind the transcribing RNA polymerase. Read More

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http://dx.doi.org/10.1093/nar/gkz260DOI Listing
April 2019
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Modulation of the helical properties of DNA: next-to-nearest neighbour effects and beyond.

Nucleic Acids Res 2019 Apr 8. Epub 2019 Apr 8.

Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology (BIST), 08028 Barcelona, Spain.

We used extensive molecular dynamics simulations to study the structural and dynamic properties of the central d(TpA) step in the highly polymorphic d(CpTpApG) tetranucleotide. Contrary to the assumption of the dinucleotide-model and its nearest neighbours (tetranucleotide-model), the properties of the central d(TpA) step change quite significantly dependent on the next-to-nearest (hexanucleotide) sequence context and in a few cases are modulated by even remote neighbours (beyond next-to-nearest from the central TpA). Our results highlight the existence of previously undescribed dynamical mechanisms for the transmission of structural information into the DNA and demonstrate the existence of certain sequences with special physical properties that can impact on the global DNA structure and dynamics. Read More

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https://academic.oup.com/nar/advance-article/doi/10.1093/nar
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http://dx.doi.org/10.1093/nar/gkz255DOI Listing
April 2019
2 Reads

A new role for Escherichia coli Dam DNA methylase in prevention of aberrant chromosomal replication.

Nucleic Acids Res 2019 Apr 8. Epub 2019 Apr 8.

Laboratory of Bacterial Genetics, Centre for DNA Fingerprinting and Diagnostics, Hyderabad 500039, India.

The Dam DNA methylase of Escherichia coli is required for methyl-directed mismatch repair, regulation of chromosomal DNA replication initiation from oriC (which is DnaA-dependent), and regulation of gene expression. Here, we show that Dam suppresses aberrant oriC-independent chromosomal replication (also called constitutive stable DNA replication, or cSDR). Dam deficiency conferred cSDR and, in presence of additional mutations (Δtus, rpoB*35) that facilitate retrograde replication fork progression, rescued the lethality of ΔdnaA mutants. Read More

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https://academic.oup.com/nar/advance-article/doi/10.1093/nar
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http://dx.doi.org/10.1093/nar/gkz242DOI Listing
April 2019
2 Reads

The crystal structure of an antiparallel chair-type G-quadruplex formed by Bromo-substituted human telomeric DNA.

Nucleic Acids Res 2019 Apr 8. Epub 2019 Apr 8.

Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong SAR, China.

Human telomeric guanine-rich DNA, which could adopt different G-quadruplex structures, plays important roles in protecting the cell from recombination and degradation. Although many of these structures were determined, the chair-type G-quadruplex structure remains elusive. Here, we present a crystal structure of the G-quadruplex composed of the human telomeric sequence d[GGGTTAGG8GTTAGGGTTAGG20G] with two dG to 8Br-dG substitutions at positions 8 and 20 with syn conformation in the K+ solution. Read More

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http://dx.doi.org/10.1093/nar/gkz221DOI Listing

Proteomic and transcriptomic experiments reveal an essential role of RNA degradosome complexes in shaping the transcriptome of Mycobacterium tuberculosis.

Nucleic Acids Res 2019 Apr 8. Epub 2019 Apr 8.

Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawińskiego 5A, Warsaw 02-106, Poland.

The phenotypic adjustments of Mycobacterium tuberculosis are commonly inferred from the analysis of transcript abundance. While mechanisms of transcriptional regulation have been extensively analysed in mycobacteria, little is known about mechanisms that shape the transcriptome by regulating RNA decay rates. The aim of the present study is to identify the core components of the RNA degradosome of M. Read More

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http://dx.doi.org/10.1093/nar/gkz251DOI Listing
April 2019
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A single-input binary counting module based on serine integrase site-specific recombination.

Nucleic Acids Res 2019 Apr 8. Epub 2019 Apr 8.

Institute of Molecular, Cell and Systems Biology, University of Glasgow, Bower Building, Glasgow G12 8QQ, Scotland.

A device that counts and records the number of events experienced by an individual cell could have many uses in experimental biology and biotechnology. Here, we report a DNA-based 'latch' that switches between two states upon each exposure to a repeated stimulus. The key component of the latch is a DNA segment whose orientation is inverted by the actions of ϕC31 integrase and its recombination directionality factor (RDF). Read More

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http://dx.doi.org/10.1093/nar/gkz245DOI Listing

Next-level riboswitch development-implementation of Capture-SELEX facilitates identification of a new synthetic riboswitch.

Nucleic Acids Res 2019 Apr 8. Epub 2019 Apr 8.

Department of Biology, TU Darmstadt, Schnittspahnstrasse 10, 64287 Darmstadt, Germany.

The development of synthetic riboswitches has always been a challenge. Although a number of interesting proof-of-concept studies have been published, almost all of these were performed with the theophylline aptamer. There is no shortage of small molecule-binding aptamers; however, only a small fraction of them are suitable for RNA engineering since a classical SELEX protocol selects only for high-affinity binding but not for conformational switching. Read More

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https://academic.oup.com/nar/advance-article/doi/10.1093/nar
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http://dx.doi.org/10.1093/nar/gkz216DOI Listing
April 2019
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Primed adaptation tolerates extensive structural and size variations of the CRISPR RNA guide in Haloarcula hispanica.

Nucleic Acids Res 2019 Apr 8. Epub 2019 Apr 8.

State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.

Recent studies on CRISPR adaptation revealed that priming is a major pathway of spacer acquisition, at least for the most prevalent type I systems. Priming is guided by a CRISPR RNA which fully/partially matches the invader DNA, but the plasticity of this RNA guide has not yet been characterized. In this study, we extensively modified the two conserved handles of a priming crRNA in Haloarcula hispanica, and altered the size of its central spacer part. Read More

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http://dx.doi.org/10.1093/nar/gkz244DOI Listing
April 2019
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High resolution discovery of chromatin interactions.

Nucleic Acids Res 2019 Apr;47(6):e35

Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA, USA.

Chromatin interaction analysis by paired-end tag sequencing (ChIA-PET) is a method for the genome-wide de novo discovery of chromatin interactions. Existing computational methods typically fail to detect weak or dynamic interactions because they use a peak-calling step that ignores paired-end linkage information. We have developed a novel computational method called Chromatin Interaction Discovery (CID) to overcome this limitation with an unbiased clustering approach for interaction discovery. Read More

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http://dx.doi.org/10.1093/nar/gkz051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6451139PMC

The G3-U70-independent tRNA recognition by human mitochondrial alanyl-tRNA synthetase.

Nucleic Acids Res 2019 Apr;47(6):3072-3085

State Key Laboratory of Molecular Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China.

Alanyl-tRNA synthetases (AlaRSs) from three domains of life predominantly rely on a single wobble base pair, G3-U70, of tRNAAla as a major determinant. However, this base pair is divergent in human mitochondrial tRNAAla, but instead with a translocated G5-U68. How human mitochondrial AlaRS (hmtAlaRS) recognizes tRNAAla, in particular, in the acceptor stem region, remains unknown. Read More

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http://dx.doi.org/10.1093/nar/gkz078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6451123PMC
April 2019
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Increased versatility despite reduced molecular complexity: evolution, structure and function of metazoan splicing factor PRPF39.

Nucleic Acids Res 2019 Apr 5. Epub 2019 Apr 5.

Institut für Chemie und Biochemie, RNA Biochemie, Freie Universität Berlin, Takustr. 6, 14195 Berlin, Germany.

In the yeast U1 snRNP the Prp39/Prp42 heterodimer is essential for early steps of spliceosome assembly. In metazoans no Prp42 ortholog exists, raising the question how the heterodimer is functionally substituted. Here we present the crystal structure of murine PRPF39, which forms a homodimer. Read More

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http://dx.doi.org/10.1093/nar/gkz243DOI Listing
April 2019
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SCRE serves as a unique synaptonemal complex fastener and is essential for progression of meiosis prophase I in mice.

Nucleic Acids Res 2019 Apr 5. Epub 2019 Apr 5.

Center for Reproductive Medicine, Shandong University, Jinan, China; The Key Laboratory of Reproductive Endocrinology of Ministry of Education, Jinan, China; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Jinan, China.

Meiosis is a specialized cell division for producing haploid gametes from diploid germ cells. During meiosis, synaptonemal complex (SC) mediates the alignment of homologs and plays essential roles in homologous recombination and therefore in promoting accurate chromosome segregation. In this study, we have identified a novel protein SCRE (synaptonemal complex reinforcing element) as a key molecule in maintaining the integrity of SC during meiosis prophase I in mice. Read More

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http://dx.doi.org/10.1093/nar/gkz226DOI Listing
April 2019
2 Reads

A unique exonuclease ExoG cleaves between RNA and DNA in mitochondrial DNA replication.

Nucleic Acids Res 2019 Apr 5. Epub 2019 Apr 5.

Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan 11529, ROC.

Replication of sufficient mitochondrial DNA (mtDNA) is essential for maintaining mitochondrial functions in mammalian cells. During mtDNA replication, RNA primers must be removed before the nascent circular DNA strands rejoin. This process involves mitochondrial RNase H1, which removes most of the RNA primers but leaves two ribonucleotides attached to the 5' end of nascent DNA. Read More

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http://dx.doi.org/10.1093/nar/gkz241DOI Listing