PubMed Central (PMC3 - NLM DTD)
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Archive of life sciences journal literature at the U.S. National Institutes of Health (NIH), developed and managed by NIH's National Center for Biotechnology Information (NCBI) in the National Library of Medicine (NLM).
Mostrando recursos 21 - 40 de 59,293
21.
TopNet: a tool for comparing biological sub-networks, correlating protein properties with topological statistics - Yu, Haiyuan; Zhu, Xiaowei; Greenbaum, Dov; Karro, John; Gerstein, Mark
Biological networks are a topic of great current interest, particularly with the publication of a number of large genome-wide interaction datasets. They are globally characterized by a variety of graph-theoretic statistics, such as the degree distribution, clustering coefficient, characteristic path length and diameter. Moreover, real protein networks are quite complex and can often be divided into many sub-networks through systematic selection of different nodes and edges. For instance, proteins can be sub-divided by expression level, length, amino-acid composition, solubility, secondary structure and function. A challenging research question is to compare the topologies of sub- networks, looking for global differences associated...
22.
The major human AP endonuclease (Ape1) is involved in the nucleotide incision repair pathway - Gros, Laurent; Ishchenko, Alexander A.; Ide, Hiroshi; Elder, Rhoderick H.; Saparbaev, Murat K.
In nucleotide incision repair (NIR), an endonuclease nicks oxidatively damaged DNA in a DNA glycosylase-independent manner, providing the correct ends for DNA synthesis coupled to the repair of the remaining 5?-dangling modified nucleotide. This mechanistic feature is distinct from DNA glycosylase-mediated base excision repair. Here we report that Ape1, the major apurinic/apyrimidinic endonuclease in human cells, is the damage- specific endonuclease involved in NIR. We show that Ape1 incises DNA containing 5,6-dihydro-2?-deoxyuridine, 5,6-dihydrothymidine, 5-hydroxy-2?-deoxyuridine, alpha-2?-deoxyadenosine and alpha-thymidine adducts, generating 3?-hydroxyl and 5?-phosphate termini. The kinetic constants indicate that Ape1-catalysed NIR activity is highly efficient. The substrate specificity and protein conformation...
23.
Echinomycin inhibits chromosomal DNA replication and embryonic development in vertebrates - May, Laurence G.; Madine, Mark A.; Waring, Michael J.
Echinomycin, a member of the quinoxaline family of antibiotics, is known to be a strong inhibitor of RNA synthesis which has been attributed to its ability to bind to double-helical DNA. Here we study the effect of echinomycin upon DNA replication using egg extracts and embryos from Xenopus laevis as well as cultured human cells. Evidence is presented that echinomycin interferes with chromatin decondensation, nuclear assembly and DNA replication. In the absence of transcription and translation, the drug specifically blocks DNA replication in both Xenopus sperm chromatin and HeLa cell nuclei in vitro. By contrast, replication of single-stranded DNA is...
24.
Coenzyme B12 riboswitches are widespread genetic control elements in prokaryotes - Nahvi, Ali; Barrick, Jeffrey E.; Breaker, Ronald R.
Recent studies have begun to reveal that numerous fundamental metabolic pathways in bacteria are regulated by riboswitches residing within certain messenger RNAs. These riboswitches selectively bind metabolites and modulate gene expression in response to changing ligand concentrations. Previously, we provided evidence that the btuB mRNAs of Escherichia coli and Salmonella typhimurium each carry a coenzyme B12-dependent riboswitch that causes repressed translation of the encoded cobalamin-transport protein at elevated coenzyme concentrations. Herein, we use a phylogenetic analysis to define a consensus sequence and secondary structure model for the ligand- binding domain of this riboswitch class. RNA structures that conform to this...
25.
Secondary structure models of the nuclear internal transcribed spacer regions and 5.8S rRNA in Calciodinelloideae (Peridiniaceae) and other dinoflagellates - Gottschling, Marc; Plötner, Jörg
Secondary structure models of the 5.8S rRNA and both internal transcribed spacers (ITS1 and ITS2) are proposed for Calciodinelloideae (Peridiniaceae) and are also plausible for other dinoflagellates. The secondary structure of the 5.8S rRNA corresponds to previously developed models, with two internal paired regions and at least one 5.8S rRNA28S rRNA interaction. A general secondary structure model of ITS1 for Calciodinelloideae (and other dinoflagellates), consisting of an open multibranch loop with three major helices, is proposed. The homology of these paired regions with those found in other taxa, published in previous studies (e.g. yeast, green algae and Platyhelmithes) remains to...
26.
Finding functional sequence elements by multiple local alignment - Frith, Martin C.; Hansen, Ulla; Spouge, John L.; Weng, Zhiping
Algorithms that detect and align locally similar regions of biological sequences have the potential to discover a wide variety of functional motifs. Two theoretical contributions to this classic but unsolved problem are presented here: a method to determine the width of the aligned motif automatically; and a technique for calculating the statistical significance of alignments, i.e. an assessment of whether the alignments are stronger than those that would be expected to occur by chance among random, unrelated sequences. Upon exploring variants of the standard Gibbs sampling technique to optimize the alignment, we discovered that simulated annealing approaches perform more efficiently....
27.
YB-1 promotes strand separation in vitro of duplex DNA containing either mispaired bases or cisplatin modifications, exhibits endonucleolytic activities and binds several DNA repair proteins - Gaudreault, Isabelle; Guay, David; Lebel, Michel
YB-1 is a multifunctional protein involved in the regulation of transcription, translation, mRNA splicing and probably DNA repair. It contains a conserved cold shock domain and it binds strongly to inverted CCAAT box of different promoters. In this study, we have found that purified YB-1 oligomerizes readily in solutions to form trimers, hexamers and oligomers of 12 molecules. The presence of ATP changed the conformation of YB-1 in such a way that only dimers were detected by gel filtration analyses. Purified YB-1 can separate different DNA duplexes containing blunt ends, 5? or 3? recessed ends, or forked structures. This strand...
28.
Detection of guanineadenine mismatches by surface plasmon resonance sensor carrying naphthyridineazaquinolone hybrid on the surface - Hagihara, Shinya; Kumasawa, Hiroyuki; Goto, Yuki; Hayashi, Gosuke; Kobori, Akio; Saito, Isao; Nakatani, Kazuhiko
We have discovered a new molecule naphthyridineazaquinolone hybrid (NptAzq) that strongly stabilized the guanine-adenine (G-A) mismatch in duplex DNA. In the presence of NptAzq, the melting temperature (Tm) of 5?-d(CTA ACG GAA TG)-3?/3?-d(GAT TGA CTT AC)-5? containing a single G-A mismatch increased by 15.4°C, whereas fully matched duplex increased its Tm only by 2.2°C. NptAzq was immobilized on the sensor surface for the surface plasmon resonance (SPR) assay to examine SPR detection of duplexes containing a G-A mismatch. Distinct SPR signals were observed when 27mer DNA containing a G-A mismatch was analyzed by the NptAzq immobilized sensor surfaces, whereas the...
29.
The last CTD repeat of the mammalian RNA polymerase II large subunit is important for its stability - Chapman, Rob D.; Palancade, Benoit; Lang, Andreas; Bensaude, Olivier; Eick, Dirk
The phosphorylation of the RNA polymerase II (Pol II) C-terminal domain (CTD) has been shown to affect the initiation, and transition to elongation of the Pol II complex. The differential phosphorylation of serines within this domain coincides with the recruitment of factors important for pre-mRNA processing and transcriptional elongation. A role for tyrosine and threonine phosphorylation has yet to be described. The discovery of kinases that express a preference for specific residues within this sequence suggests a mechanism for the controlled recruitment and displacement of CTD-interacting partners during the transcription cycle. The last CTD repeat (CTD52) contains unique interaction sites...
30.
Structural and biochemical analyses of hemimethylated DNA binding by the SeqA protein - Fujikawa, Norie; Kurumizaka, Hitoshi; Nureki, Osamu; Tanaka, Yoshinori; Yamazoe, Mitsuyoshi; Hiraga, Sota; Yokoyama, Shigeyuki
The Escherichia coli SeqA protein recognizes the 11 hemimethylated G-mA-T-C sites in the oriC region of the chromosome, and prevents replication over-initiation within one cell cycle. The crystal structure of the SeqA C-terminal domain with hemimethylated DNA revealed the N6-methyladenine recognition mechanism; however, the mechanism of discrimination between the hemimethylated and fully methylated states has remained elusive. In the present study, we performed mutational analyses of hemimethylated G-mA-T-C sequences with the minimal DNA-binding domain of SeqA (SeqA71181), and found that SeqA71181 specifically binds to hemimethylated DNA containing a sequence with a mismatched mA:G base pair [G-mA(:G)-T-C] as efficiently as the...
31.
CIRCE is not involved in heat-dependent transcription of groESL but in stabilization of the mRNA 5?-end in Rhodobacter capsulatus - Jäger, Stephanie; Jäger, Andreas; Klug, Gabriele
The CIRCE element, an inverted DNA repeat, is known to be involved in the temperature-dependent regulation of genes for heat shock proteins in a variety of organisms. The CIRCE element was identified as the target for the HrcA protein, which represses transcription of heat shock genes under normal growth temperature. Our data reveal that the CIRCE element is not involved in the temperature-dependent transcription of the groESL genes in Rhodobacter capsulatus. Apparently, R.capsulatus does not harbour an HrcA protein. The mechanisms of heat shock regulation of the groESL genes in R.capsulatus therefore diverge significantly from the regulatory pathway identified in...
32.
Hydration of short DNA, RNA and 2?-OMe oligonucleotides determined by osmotic stressing - Rozners, Eriks; Moulder, Janelle
Studies on hydration are important for better understanding of structure and function of nucleic acids. We compared the hydration of self-complementary DNA, RNA and 2?-O-methyl (2?-OMe) oligonucleotides GCGAAUUCGC, (UA)6 and (CG)3 using the osmotic stressing method. The number of water molecules released upon melting of oligonucleotide duplexes, ?nW, was calculated from the dependence of melting temperature on water activity and the enthalpy, both measured with UV thermal melting experiments. The water activity was changed by addition of ethylene glycol, glycerol and acetamide as small organic co-solutes. The ?nW was 34 for RNA duplexes and 23 for DNA and 2?-OMe duplexes....
33.
ARC-1, a sequence element complementary to an internal 18S rRNA segment, enhances translation efficiency in plants when present in the leader or intercistronic region of mRNAs - Akbergenov, R. Zh.; Zhanybekova, S. Sh.; Kryldakov, R. V.; Zhigailov, A.; Polimbetova, N. S.; Hohn, T.; Iskakov, B. K.
The sequences of different plant viral leaders with known translation enhancer ability show partial complementarity to the central region of 18S rRNA. Such complementarity might serve as a means to attract 40S ribosomal subunits and explain in part the translation-enhancing property of these sequences. To verify this notion, we designed ?-glucuronidase (GUS) mRNAs differing only in the nature of 10 nt inserts in the center of their 41 base leaders. These were complementary to consecutive domains of plant 18S rRNA. Sucrose gradient analysis revealed that leaders with inserts complementary to regions 11051114 and 11151124 (ARC-1) of plant 18S rRNA bound...
34.
Modifications of the 3?-UTR stemloop of infectious bursal disease virus are allowed without influencing replication or virulence - Boot, Hein J.; Pritz-Verschuren, Sylvia B. E.
Many questions regarding the initiation of replication and translation of the segmented, double-stranded RNA genome of infectious bursal disease virus (IBDV) remain to be solved. Computer analysis shows that the non-polyadenylated extreme 3?-untranslated regions (UTRs) of the coding strand of both genomic segments are able to fold into a single stemloop structure. To assess the determinants for a functional 3?-UTR, we mutagenized the 3?-UTR stemloop structure of the B-segment. Rescue of infectious virus from mutagenized cDNA plasmids was impaired in all cases. However, after one passage, the replication kinetics of these viruses were restored. Sequence analysis revealed that additional mutations...
35.
The nature of actinomycin D binding to d(AACCAXYG) sequence motifs - Chen, Fu-Ming; Sha, Feng; Chin, Ko-Hsin; Chou, Shan-Ho
Earlier studies by others had indicated that actinomycin D (ACTD) binds well to d(AACCATAG) and the end sequence TAG-3? is essential for its strong binding. In an effort to verify these assertions and to uncover other possible strong ACTD binding sequences as well as to elucidate the nature of their binding, systematic studies have been carried out with oligomers of d(AACCAXYG) sequence motifs, where X and Y can be any DNA base. The results indicate that in addition to TAG-3?, oligomers ending with XAG-3? and XCG-3? all provide binding constants ?1 × 107 M1 and even sequences ending with XTG-3?...
36.
The guanine-rich fragile X chromosome repeats are reluctant to form tetraplexes - Fojtík, Petr; Kejnovská, Iva; Vorlí?ková, Michaela
Using circular dichroism spectroscopy, UV absorption spectroscopy and polyacrylamide gel electrophoresis, we studied conformational properties of guanine-rich DNA strands of the fragile X chromosome repeats d(GGC)n, d(GCG)n and d(CGG)n, with n = 2, 4, 8 and 16. These strands are generally considered in the literature to form guanine tetraplexes responsible for the repeat expansion. However, we show in this paper that the repeats are reluctant to form tetraplexes. At physiological concentrations of either Na+ or K+ ions, the hexamers and dodecamers associate to form homoduplexes and the longer repeats generate homoduplexes and hairpins. The tetraplexes are rarely observed being relatively...
37.
Local homology recognition and distance measures in linear time using compressed amino acid alphabets - Edgar, Robert C.
Methods for discovery of local similarities and estimation of evolutionary distance by identifying k-mers (contiguous subsequences of length k) common to two sequences are described. Given unaligned sequences of length L, these methods have O(L) time complexity. The ability of compressed amino acid alphabets to extend these techniques to distantly related proteins was investigated. The performance of these algorithms was evaluated for different alphabets and choices of k using a test set of 1848 pairs of structurally alignable sequences selected from the FSSP database. Distance measures derived from k-mer counting were found to correlate well with percentage identity derived from...
38.
Telomerase downregulation induced by the G-quadruplex ligand 12459 in A549 cells is mediated by hTERT RNA alternative splicing - Gomez, Dennis; Lemarteleur, Thibault; Lacroix, Laurent; Mailliet, Patrick; Mergny, Jean-Louis; Riou, Jean-François
Ligand 12459, a potent G-quadruplex-interacting agent that belongs to the triazine series, was previously shown to downregulate telomerase activity in the human A549 lung carcinoma cell line. We show here that the downregulation of telomerase activity is caused by an alteration of the hTERT splicing pattern induced by 12459, i.e. an almost complete disappearance of the active (+?,+?) transcript and an over-expression of the inactive ? transcript. Spliced intron 6 forming the ? hTERT transcript contained several tracks of G-rich sequences able to form G-quadruplexes. By using a specific PCR-stop assay, we show that 12459 is able to stabilize the...
39.
Drosophila RNase Z processes mitochondrial and nuclear pre-tRNA 3? ends in vivo - Dubrovsky, Edward B.; Dubrovskaya, Veronica A.; Levinger, Louis; Schiffer, Steffen; Marchfelder, Anita
Although correct tRNA 3? ends are crucial for protein biosynthesis, generation of mature tRNA 3? ends in eukaryotes is poorly understood and has so far only been investigated in vitro. We report here for the first time that eukaryotic tRNA 3? end maturation is catalysed by the endonuclease RNase Z in vivo. Silencing of the JhI-1 gene (RNase Z homolog) in vivo with RNAi in Drosophila S2 cultured cells causes accumulation of nuclear and mitochondrial pre-tRNAs, suggesting that JhI-1 encodes both forms of the tRNA 3? endonuclease RNase Z, and establishing its biological role in endonucleolytic tRNA 3? end processing....
40.
Computational inference of transcriptional regulatory networks from expression profiling and transcription factor binding site identification - Haverty, Peter M.; Hansen, Ulla; Weng, Zhiping
We have developed a computational method for transcriptional regulatory network inference, CARRIE (Computational Ascertainment of Regu latory Relationships Inferred from Expression), which combines microarray and promoter sequence analysis. CARRIE uses sources of data to identify the transcription factors (TFs) that regulate gene expression changes in response to a stimulus and generates testable hypotheses about the regulatory network connecting these TFs to the genes they regulate. The promoter analysis component of CARRIE, ROVER (Relative OVER-abundance of cis-elements), is highly accurate at detecting the TFs that regulate the response to a stimulus. ROVER also predicts which genes are regulated by each of...
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