Journal of Nucleic Acids最新文献

{"title":"Convenient and scalable synthesis of fmoc-protected Peptide nucleic Acid backbone.","authors":"Trevor A Feagin, Nirmal I Shah, Jennifer M Heemstra","doi":"10.1155/2012/354549","DOIUrl":"10.1155/2012/354549","url":null,"abstract":"<p><p>The peptide nucleic acid backbone Fmoc-AEG-OBn has been synthesized via a scalable and cost-effective route. Ethylenediamine is mono-Boc protected, then alkylated with benzyl bromoacetate. The Boc group is removed and replaced with an Fmoc group. The synthesis was performed starting with 50 g of Boc anhydride to give 31 g of product in 32% overall yield. The Fmoc-protected PNA backbone is a key intermediate in the synthesis of nucleobase-modified PNA monomers. Thus, improved access to this molecule is anticipated to facilitate future investigations into the chemical properties and applications of nucleobase-modified PNA.</p>","PeriodicalId":16575,"journal":{"name":"Journal of Nucleic Acids","volume":"2012 ","pages":"354549"},"PeriodicalIF":2.3,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3400375/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30802001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alternative Splicing of Fibroblast Growth Factor Receptor IgIII Loops in Cancer.","authors":"Klaus Holzmann,&nbsp;Thomas Grunt,&nbsp;Christine Heinzle,&nbsp;Sandra Sampl,&nbsp;Heinrich Steinhoff,&nbsp;Nicole Reichmann,&nbsp;Miriam Kleiter,&nbsp;Marlene Hauck,&nbsp;Brigitte Marian","doi":"10.1155/2012/950508","DOIUrl":"https://doi.org/10.1155/2012/950508","url":null,"abstract":"<p><p>Alternative splicing of the IgIII loop of fibroblast growth factor receptors (FGFRs) 1-3 produces b- and c-variants of the receptors with distinctly different biological impact based on their distinct ligand-binding spectrum. Tissue-specific expression of these splice variants regulates interactions in embryonic development, tissue maintenance and repair, and cancer. Alterations in FGFR2 splicing are involved in epithelial mesenchymal transition that produces invasive, metastatic features during tumor progression. Recent research has elucidated regulatory factors that determine the splice choice both on the level of exogenous signaling events and on the RNA-protein interaction level. Moreover, methodology has been developed that will enable the in depth analysis of splicing events during tumorigenesis and provide further insight on the role of FGFR 1-3 IIIb and IIIc in the pathophysiology of various malignancies. This paper aims to summarize expression patterns in various tumor types and outlines possibilities for further analysis and application.</p>","PeriodicalId":16575,"journal":{"name":"Journal of Nucleic Acids","volume":"2012 ","pages":"950508"},"PeriodicalIF":2.3,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/950508","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30353072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"p53 Family: Role of Protein Isoforms in Human Cancer.","authors":"Jinxiong Wei,&nbsp;Elena Zaika,&nbsp;Alexander Zaika","doi":"10.1155/2012/687359","DOIUrl":"https://doi.org/10.1155/2012/687359","url":null,"abstract":"<p><p>TP53, TP63, and TP73 genes comprise the p53 family. Each gene produces protein isoforms through multiple mechanisms including extensive alternative mRNA splicing. Accumulating evidence shows that these isoforms play a critical role in the regulation of many biological processes in normal cells. Their abnormal expression contributes to tumorigenesis and has a profound effect on tumor response to curative therapy. This paper is an overview of isoform diversity in the p53 family and its role in cancer.</p>","PeriodicalId":16575,"journal":{"name":"Journal of Nucleic Acids","volume":"2012 ","pages":"687359"},"PeriodicalIF":2.3,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/687359","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30216559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dioxaphosphorinane-constrained nucleic Acid dinucleotides as tools for structural tuning of nucleic acids.","authors":"Dan-Andrei Catana,&nbsp;Brice-Loïc Renard,&nbsp;Marie Maturano,&nbsp;Corinne Payrastre,&nbsp;Nathalie Tarrat,&nbsp;Jean-Marc Escudier","doi":"10.1155/2012/215876","DOIUrl":"https://doi.org/10.1155/2012/215876","url":null,"abstract":"<p><p>We describe a rational approach devoted to modulate the sugar-phosphate backbone geometry of nucleic acids. Constraints were generated by connecting one oxygen of the phosphate group to a carbon of the sugar moiety. The so-called dioxaphosphorinane rings were introduced at key positions along the sugar-phosphate backbone allowing the control of the six-torsion angles α to ζ defining the polymer structure. The syntheses of all the members of the D-CNA family are described, and we emphasize the effect on secondary structure stabilization of a couple of diastereoisomers of α,β-D-CNA exhibiting wether B-type canonical values or not.</p>","PeriodicalId":16575,"journal":{"name":"Journal of Nucleic Acids","volume":"2012 ","pages":"215876"},"PeriodicalIF":2.3,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/215876","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31047772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural and Functional Characterization of RecG Helicase under Dilute and Molecular Crowding Conditions.","authors":"Sarika Saxena,&nbsp;Satoru Nagatoishi,&nbsp;Daisuke Miyoshi,&nbsp;Naoki Sugimoto","doi":"10.1155/2012/392039","DOIUrl":"https://doi.org/10.1155/2012/392039","url":null,"abstract":"<p><p>In an ATP-dependent reaction, the Escherichia coli RecG helicase unwinds DNA junctions in vitro. We present evidence of a unique protein conformational change in the RecG helicase from an α-helix to a β-strand upon an ATP binding under dilute conditions using circular dichroism (CD) spectroscopy. In contrast, under molecular crowding conditions, the α-helical conformation was stable even upon an ATP binding. These distinct conformational behaviors were observed to be independent of Na(+) and Mg(2+). Interestingly, CD measurements demonstrated that the spectra of a frayed duplex decreased with increasing of the RecG concentration both under dilute and molecular crowding conditions in the presence of ATP, suggesting that RecG unwound the frayed duplex. Our findings raise the possibility that the α-helix and β-strand forms of RecG are a preactive and an active structure with the helicase activity, respectively.</p>","PeriodicalId":16575,"journal":{"name":"Journal of Nucleic Acids","volume":"2012 ","pages":"392039"},"PeriodicalIF":2.3,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/392039","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30856616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"UvrD Participation in Nucleotide Excision Repair Is Required for the Recovery of DNA Synthesis following UV-Induced Damage in Escherichia coli.","authors":"Kelley N Newton,&nbsp;Charmain T Courcelle,&nbsp;Justin Courcelle","doi":"10.1155/2012/271453","DOIUrl":"https://doi.org/10.1155/2012/271453","url":null,"abstract":"<p><p>UvrD is a DNA helicase that participates in nucleotide excision repair and several replication-associated processes, including methyl-directed mismatch repair and recombination. UvrD is capable of displacing oligonucleotides from synthetic forked DNA structures in vitro and is essential for viability in the absence of Rep, a helicase associated with processing replication forks. These observations have led others to propose that UvrD may promote fork regression and facilitate resetting of the replication fork following arrest. However, the molecular activity of UvrD at replication forks in vivo has not been directly examined. In this study, we characterized the role UvrD has in processing and restoring replication forks following arrest by UV-induced DNA damage. We show that UvrD is required for DNA synthesis to recover. However, in the absence of UvrD, the displacement and partial degradation of the nascent DNA at the arrested fork occur normally. In addition, damage-induced replication intermediates persist and accumulate in uvrD mutants in a manner that is similar to that observed in other nucleotide excision repair mutants. These data indicate that, following arrest by DNA damage, UvrD is not required to catalyze fork regression in vivo and suggest that the failure of uvrD mutants to restore DNA synthesis following UV-induced arrest relates to its role in nucleotide excision repair.</p>","PeriodicalId":16575,"journal":{"name":"Journal of Nucleic Acids","volume":"2012 ","pages":"271453"},"PeriodicalIF":2.3,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/271453","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30969648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artificial specific binders directly recovered from chemically modified nucleic acid libraries.","authors":"Yuuya Kasahara, Masayasu Kuwahara","doi":"10.1155/2012/156482","DOIUrl":"10.1155/2012/156482","url":null,"abstract":"<p><p>Specific binders comprised of nucleic acids, that is, RNA/DNA aptamers, are attractive functional biopolymers owing to their potential broad application in medicine, food hygiene, environmental analysis, and biological research. Despite the large number of reports on selection of natural DNA/RNA aptamers, there are not many examples of direct screening of chemically modified nucleic acid aptamers. This is because of (i) the inferior efficiency and accuracy of polymerase reactions involving transcription/reverse-transcription of modified nucleotides compared with those of natural nucleotides, (ii) technical difficulties and additional time and effort required when using modified nucleic acid libraries, and (iii) ambiguous efficacies of chemical modifications in binding properties until recently; in contrast, the effects of chemical modifications on biostability are well studied using various nucleotide analogs. Although reports on the direct screening of a modified nucleic acid library remain in the minority, chemical modifications would be essential when further functional expansion of nucleic acid aptamers, in particular for medical and biological uses, is considered. This paper focuses on enzymatic production of chemically modified nucleic acids and their application to random screenings. In addition, recent advances and possible future research are also described.</p>","PeriodicalId":16575,"journal":{"name":"Journal of Nucleic Acids","volume":"2012 ","pages":"156482"},"PeriodicalIF":2.3,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3472525/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30998752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional Annotation of Small Noncoding RNAs Target Genes Provides Evidence for a Deregulated Ubiquitin-Proteasome Pathway in Spinocerebellar Ataxia Type 1.","authors":"Stephan Persengiev,&nbsp;Ivanela Kondova,&nbsp;Ronald E Bontrop","doi":"10.1155/2012/672536","DOIUrl":"https://doi.org/10.1155/2012/672536","url":null,"abstract":"<p><p>Spinocerebellar ataxia type 1 (SCA1) is a neurodegenerative disorder caused by the expansion of CAG repeats in the ataxin 1 (ATXN1) gene. In affected cerebellar neurons of patients, mutant ATXN1 accumulates in ubiquitin-positive nuclear inclusions, indicating that protein misfolding is involved in SCA1 pathogenesis. In this study, we functionally annotated the target genes of the small noncoding RNAs (ncRNAs) that were selectively activated in the affected brain compartments. The primary targets of these RNAs, which exhibited a significant enrichment in the cerebellum and cortex of SCA1 patients, were members of the ubiquitin-proteasome system. Thus, we identified and functionally annotated a plausible regulatory pathway that may serve as a potential target to modulate the outcome of neurodegenerative diseases.</p>","PeriodicalId":16575,"journal":{"name":"Journal of Nucleic Acids","volume":"2012 ","pages":"672536"},"PeriodicalIF":2.3,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/672536","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31000342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expansion of the genetic alphabet: unnatural nucleobases and their applications.","authors":"Subhendu Sekhar Bag,&nbsp;Jennifer M Heemstra,&nbsp;Yoshio Saito,&nbsp;David M Chenoweth","doi":"10.1155/2012/718582","DOIUrl":"https://doi.org/10.1155/2012/718582","url":null,"abstract":"Nucleic acids are essential biomolecules that encode all of the information necessary for life. Specific pairing of A with T (or U) and C with G during replication, transcription, and translation is the key to effective transmission of genetic information between generations, as well as accurate conversion of genetic information into protein sequence. Given the magnitude of the tasks orchestrated by the Watson-Crick base pairing, it is striking to consider that biological systems accomplish these tasks using only four nucleobases. Realizing the powerful nature of base-pair recognition, researchers have been inspired to ask the question of whether the genetic code can be artificially expanded to generate biological systems having novel functions. It was this question that led Alex Rich in 1962 to propose the concept of orthogonal base pairing between iso-G and iso-C and inspired Professor Steven A. Benner in the late 1980s to expand the genetic alphabet from four to six letters. Benner's early research focused on the development of new base pairs having hydrogen bonding patterns orthogonal to those in the canonical Watson-Crick base pairs. In 1994, Professor Eric T. Kool opened a new functional dimension with the creation of nonhydrogen bonding unnatural nucleobase surrogates. \u0000 \u0000Expansion of the genetic alphabet has dramatically increased the functional potential of DNA, for example, by enabling site-directed oligonucleotide labeling and in vitro selections with oligonucleotides having increased chemical diversity. Translation of an expanded DNA alphabet into RNA is a challenging task, but one which has potential to give rise to semisynthetic organisms with increased biodiversity. This special issue highlights recent accomplishments at the interface of organic chemistry and molecular biology which hold promise to further expand the potential of nucleic acids having unnatural nucleobases. Specifically, the reports in this special issue focus on the synthesis of unnatural nucleobases and nucleic acid backbones, the exploration of their structure and duplex stabilizing ability, and the polymerase mediated replication and transcription of DNA containing unnatural nucleobases. \u0000 \u0000T. Lonnberg and a coworker report the synthesis and study of a bis(pyrazolyl)purine ribonucleoside having increased hydrophobic surface area and the ability to form complex with metal ions. The hydrogen bonding pattern of this nucleoside makes it complementary to thymine and uridine. The authors demonstrate that the bis(pyrazolyl) nucleobase is capable of forming a Pd2+-mediated base pair with uridine in the monomeric state. When incorporated into an oligonucleotide, the bis(pyrazolyl) nucleobase stabilizes DNA duplexes when paired with thymine, but this stabilization appears to result from increased π-stacking interactions rather than metal complexation. These studies open the door to applications using unnatural nucleobases to increase the binding affinity of probes and the","PeriodicalId":16575,"journal":{"name":"Journal of Nucleic Acids","volume":"2012 ","pages":"718582"},"PeriodicalIF":2.3,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/718582","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31155664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Features of \"All LNA\" Duplexes Showing a New Type of Nucleic Acid Geometry.","authors":"Charlotte Förster,&nbsp;André Eichert,&nbsp;Dominik Oberthür,&nbsp;Christian Betzel,&nbsp;Reinhard Geßner,&nbsp;Andreas Nitsche,&nbsp;Jens P Fürste","doi":"10.1155/2012/156035","DOIUrl":"https://doi.org/10.1155/2012/156035","url":null,"abstract":"<p><p>\"Locked nucleic acids\" (LNAs) belong to the backbone-modified nucleic acid family. The 2'-O,4'-C-methylene-β-D-ribofuranose nucleotides are used for single or multiple substitutions in RNA molecules and thereby introduce enhanced bio- and thermostability. This renders LNAs powerful tools for diagnostic and therapeutic applications. RNA molecules maintain the overall canonical A-type conformation upon substitution of single or multiple residues/nucleotides by LNA monomers. The structures of \"all\" LNA homoduplexes, however, exhibit significant differences in their overall geometry, in particular a decreased twist, roll and propeller twist. This results in a widening of the major groove, a decrease in helical winding, and an enlarged helical pitch. Therefore, the LNA duplex structure can no longer be described as a canonical A-type RNA geometry but can rather be brought into proximity to other backbone-modified nucleic acids, like glycol nucleic acids or peptide nucleic acids. LNA-modified nucleic acids provide thus structural and functional features that may be successfully exploited for future application in biotechnology and drug discovery.</p>","PeriodicalId":16575,"journal":{"name":"Journal of Nucleic Acids","volume":"2012 ","pages":"156035"},"PeriodicalIF":2.3,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/156035","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30665542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}