scholarly journals Design and Synthesis of Heterocyclic Cations for Specific DNA Recognition: From AT-Rich to Mixed-Base-Pair DNA Sequences

2014 ◽  
Vol 79 (3) ◽  
pp. 852-866 ◽  
Author(s):  
Yun Chai ◽  
Ananya Paul ◽  
Michael Rettig ◽  
W. David Wilson ◽  
David W. Boykin
Keyword(s):  
Dna Sequences ◽  
Base Pair ◽  
Dna Recognition ◽  
Design And Synthesis ◽  
Heterocyclic Cations

ChemInform Abstract: Design and Synthesis of Heterocyclic Cations for Specific DNA Recognition: From AT-Rich to Mixed-Base-Pair DNA Sequences.

ChemInform ◽  
2014 ◽  
Vol 45 (29) ◽  
pp. no-no
Author(s):  
Yun Chai ◽  
Ananya Paul ◽  
Michael Rettig ◽  
W. David Wilson ◽  
David W. Boykin
Keyword(s):  
Dna Sequences ◽  
Base Pair ◽  
Dna Recognition ◽  
Design And Synthesis ◽  
Heterocyclic Cations

scholarly journals The structure of ORC–Cdc6 on an origin DNA reveals the mechanism of ORC activation by the replication initiator Cdc6

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Xiang Feng ◽  
Yasunori Noguchi ◽  
Marta Barbon ◽  
Bruce Stillman ◽  
Christian Speck ◽  
...  
Keyword(s):  
Dna Sequences ◽  
Origin Recognition Complex ◽  
Molecular Level ◽  
Dna Recognition ◽  
Winged Helix ◽  
Replicative Helicase ◽  
The Core ◽  
Α Helix ◽  
Replication Initiator ◽  
Winged Helix Domain

AbstractThe Origin Recognition Complex (ORC) binds to sites in chromosomes to specify the location of origins of DNA replication. The S. cerevisiae ORC binds to specific DNA sequences throughout the cell cycle but becomes active only when it binds to the replication initiator Cdc6. It has been unclear at the molecular level how Cdc6 activates ORC, converting it to an active recruiter of the Mcm2-7 hexamer, the core of the replicative helicase. Here we report the cryo-EM structure at 3.3 Å resolution of the yeast ORC–Cdc6 bound to an 85-bp ARS1 origin DNA. The structure reveals that Cdc6 contributes to origin DNA recognition via its winged helix domain (WHD) and its initiator-specific motif. Cdc6 binding rearranges a short α-helix in the Orc1 AAA+ domain and the Orc2 WHD, leading to the activation of the Cdc6 ATPase and the formation of the three sites for the recruitment of Mcm2-7, none of which are present in ORC alone. The results illuminate the molecular mechanism of a critical biochemical step in the licensing of eukaryotic replication origins.

Tc, an unusual promoter element required for constitutive transcription of the yeast HIS3 gene

1990 ◽  
Vol 10 (9) ◽  
pp. 4447-4455
Author(s):  
S Mahadevan ◽  
K Struhl
Keyword(s):  
Transcription Factor ◽  
Dna Sequences ◽  
Base Pair ◽  
Point Mutations ◽  
Proximal Promoter ◽  
Promoter Element ◽  
Tata Element ◽  
Typical Sequence ◽  
His3 Gene ◽  
Transcriptional Stimulation

Tc is the proximal promoter element required for constitutive his3 transcription that occurs in the absence of the canonical TATA element (TR) and is initiated from the +1 site. The TC element, unlike TR, does not respond to transcriptional stimulation by the GCN4 or GAL4 activator protein. Analysis of deletion, substitution, and point mutations indicates that Tc mapped between nucleotides -54 and -83 and is a sequence-dependent element because it could not be functionally replaced by other DNA sequences. However, in contrast to the behavior of typical promoter elements, it was surprisingly difficult to eliminate Tc function by base pair substitutions. Of 15 derivatives averaging four substitutions in the Tc region and representing 40% of all possible single changes, only 1 inactivated the Tc element. Moreover, the phenotypes of mutant and hybrid elements indicated that inactivation of Tc required multiple changes. The spacing between Tc and the initiation region could be varied over a 30-base-pair range without significantly affecting the level of transcription from the +1 site. From these results, we consider it possible that Tc may not interact with TFIID or some other typical sequence-specific transcription factor, but instead might influence transcription, either directly or indirectly, by its DNA structure.

Design and Synthesis of a Peptide That Binds Specific DNA Sequences through Simultaneous Interaction in the Major and in the Minor Groove

2001 ◽  
Vol 113 (24) ◽  
pp. 4859-4861 ◽  
Author(s):  
M. Eugenio Vázquez ◽  
Ana M. Caamaño ◽  
José Martínez-Costas ◽  
Luis Castedo ◽  
José L. Mascareñas
Keyword(s):  
Dna Sequences ◽  
Minor Groove ◽  
Design And Synthesis

scholarly journals Theoretical modelling of epigenetically modified DNA sequences

F1000Research ◽  
2015 ◽  
Vol 4 ◽  
pp. 52 ◽  
Author(s):  
Alexandra Teresa Pires Carvalho ◽  
Maria Leonor Gouveia ◽  
Charan Raju Kanna ◽  
Sebastian K. T. S. Wärmländer ◽  
Jamie Platts ◽  
...  
Keyword(s):  
Molecular Mechanics ◽  
Dna Sequences ◽  
Base Pair ◽  
Density Functional ◽  
Epigenetic Modifications ◽  
Theoretical Modelling ◽  
Sugar Phosphate ◽  
Base Pairs ◽  
Phosphate Backbone ◽  
Modified Dna

We report herein a set of calculations designed to examine the effects of epigenetic modifications on the structure of DNA. The incorporation of methyl, hydroxymethyl, formyl and carboxy substituents at the 5-position of cytosine is shown to hardly affect the geometry of CG base pairs, but to result in rather larger changes to hydrogen-bond and stacking binding energies, as predicted by dispersion-corrected density functional theory (DFT) methods. The same modifications within double-stranded GCG and ACA trimers exhibit rather larger structural effects, when including the sugar-phosphate backbone as well as sodium counterions and implicit aqueous solvation. In particular, changes are observed in the buckle and propeller angles within base pairs and the slide and roll values of base pair steps, but these leave the overall helical shape of DNA essentially intact. The structures so obtained are useful as a benchmark of faster methods, including molecular mechanics (MM) and hybrid quantum mechanics/molecular mechanics (QM/MM) methods. We show that previously developed MM parameters satisfactorily reproduce the trimer structures, as do QM/MM calculations which treat bases with dispersion-corrected DFT and the sugar-phosphate backbone with AMBER. The latter are improved by inclusion of all six bases in the QM region, since a truncated model including only the central CG base pair in the QM region is considerably further from the DFT structure. This QM/MM method is then applied to a set of double-stranded DNA heptamers derived from a recent X-ray crystallographic study, whose size puts a DFT study beyond our current computational resources. These data show that still larger structural changes are observed than in base pairs or trimers, leading us to conclude that it is important to model epigenetic modifications within realistic molecular contexts.

scholarly journals A set of experimentally validated, mutually orthogonal primers for combinatorially specifying genetic components

2018 ◽  
Vol 3 (1) ◽  
Author(s):  
Subu K Subramanian ◽  
William P Russ ◽  
Rama Ranganathan
Keyword(s):  
Synthetic Biology ◽  
High Throughput ◽  
Dna Sequences ◽  
Gene Synthesis ◽  
Modular Architecture ◽  
Design And Synthesis ◽  
Genetic Components ◽  
Polymerase Chain ◽  
Polymerase Chain Reaction Primers ◽  
Microarray Chips

Abstract The design and synthesis of novel genes and deoxyribonucleic acid (DNA) sequences is a central technique in synthetic biology. Current methods of high throughput gene synthesis use pooled oligonucleotides obtained from custom-designed DNA microarray chips, and rely on orthogonal (non-interacting) polymerase chain reaction primers to specifically de-multiplex, by amplification, the precise subset of oligonucleotides necessary to assemble a full length gene. The availability of a large validated set of mutually orthogonal primers is therefore a crucial reagent for high-throughput gene synthesis. Here, we present a set of 166 20-nucleotide primers that are experimentally verified to be non-interacting, capable of specifying 13 695 unique genes. These primers represent a valuable resource to the synthetic biology community for specifying genetic components that can be assembled through a scalable and modular architecture.

Bovine papilloma virus contains an activator of gene expression at the distal end of the early transcription unit

1983 ◽  
Vol 3 (6) ◽  
pp. 1108-1122
Author(s):  
M Lusky ◽  
L Berg ◽  
H Weiher ◽  
M Botchan
Keyword(s):  
Thymidine Kinase ◽  
Dna Sequences ◽  
Base Pair ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
Stable Transformation ◽  
High Molecular Weight Dna ◽  
Papilloma Virus ◽  
Recombinant Plasmids ◽  
Bovine Papilloma Virus

Bovine papilloma virus (BPV) contains a cis-acting DNA element which can enhance transcription of distal promoters. Utilizing both direct and indirect transient transfection assays, we showed that a 59-base-pair DNA sequence from the BPV genome could activate the simian virus 40 promoter from distances exceeding 2.5 kilobases and in an orientation-independent manner. In contrast to the promoter 5'-proximal localization of other known viral activators, this element was located immediately 3' to the early polyadenylation signal in the BPV genome. Deletion of these sequences from the BPV genome inactivated the transforming ability of BPV recombinant plasmids. Orientation-independent reinsertion of this 59-base-pair sequence, or alternatively of activator DNA sequences from simian virus 40 or polyoma virus, restored the transforming activity of the BPV recombinant plasmids. Furthermore, the stable transformation frequency of the herpes simplex virus type 1 thymidine kinase gene was enhanced when linked to restriction fragments of BPV DNA which included the defined activator element. This enhancement was orientation independent with respect to the thymidine kinase promoter. The enhancement also appeared to be unrelated to the establishment of the recombinant plasmids as episomes, since in transformed cells these sequences are found linked to high-molecular-weight DNA. We propose that the enhancement of stable transformation frequencies and the activation of transcription units are in this case alternate manifestations of the same biochemical events.

scholarly journals Reprogrammable Recognition Codes in Bicoid Homeodomain-DNA Interaction

2000 ◽  
Vol 20 (20) ◽  
pp. 7673-7684 ◽  
Author(s):  
Vrushank Dave ◽  
Chen Zhao ◽  
Fan Yang ◽  
Chang-Shung Tung ◽  
Jun Ma
Keyword(s):  
Dna Sequences ◽  
Human Disease ◽  
Dna Recognition ◽  
Dna Interaction ◽  
Morphogenetic Protein ◽  
Different Types ◽  
Disease Protein

ABSTRACT We describe experiments to determine how the homeodomain of the Drosophila morphogenetic protein Bicoid recognizes different types of DNA sequences found in natural enhancers. Our chemical footprint analyses reveal that the Bicoid homeodomain makes both shared and distinct contacts with a consensus site A1 (TAATCC) and a nonconsensus site X1 (TAAGCT). In particular, the guanine of X1 at position 4 (TAAGCT) is protected by Bicoid homeodomain. We provide further evidence suggesting that the unique arginine at position 54 (Arg 54) of the Bicoid homeodomain enables the protein to recognize X1 by specifically interacting with this position 4 guanine. We also describe experiments to analyze the contribution of artificially introduced Arg 54 to DNA recognition by other Bicoid-related homeodomains, including that from the human disease protein Pitx2. Our experiments demonstrate that the role of Arg 54 varies depending on the exact homeodomain framework and DNA sequences. Together, our results suggest that Bicoid and its related homeodomains utilize distinct recognition codes to interact with different DNA sequences, underscoring the need to study DNA recognition by Bicoid-class homeodomains in an individualized manner.

scholarly journals Total Synthesis of a Functional Designer Eukaryotic Chromosome

Science ◽  
2014 ◽  
Vol 344 (6179) ◽  
pp. 55-58 ◽  
Author(s):  
Narayana Annaluru ◽  
Héloïse Muller ◽  
Leslie A. Mitchell ◽  
Sivaprakash Ramalingam ◽  
Giovanni Stracquadanio ◽  
...  
Keyword(s):  
Total Synthesis ◽  
Base Pair ◽  
Stop Codon ◽  
Bacterial Genomes ◽  
Transfer Rnas ◽  
Eukaryotic Chromosome ◽  
Design And Synthesis ◽  
Biochemical Pathways ◽  
Chromosome Iii ◽  
Subtelomeric Regions

Rapid advances in DNA synthesis techniques have made it possible to engineer viruses, biochemical pathways and assemble bacterial genomes. Here, we report the synthesis of a functional 272,871–base pair designer eukaryotic chromosome, synIII, which is based on the 316,617–base pair native Saccharomyces cerevisiae chromosome III. Changes to synIII include TAG/TAA stop-codon replacements, deletion of subtelomeric regions, introns, transfer RNAs, transposons, and silent mating loci as well as insertion of loxPsym sites to enable genome scrambling. SynIII is functional in S. cerevisiae. Scrambling of the chromosome in a heterozygous diploid reveals a large increase in a-mater derivatives resulting from loss of the MATα allele on synIII. The complete design and synthesis of synIII establishes S. cerevisiae as the basis for designer eukaryotic genome biology.

Abstract 3219: Heterocyclic cations: Highlighting the importance of selectivity in biologically relevant quadruplex DNA recognition and binding

2010 ◽  
Author(s):  
Caterina Musetti ◽  
Arvind Kumar ◽  
Mohamed A. Ismail ◽  
Lorena Lucatello ◽  
Manoj Munde ◽  
...  
Keyword(s):  
Dna Recognition ◽  
Quadruplex Dna ◽  
Biologically Relevant ◽  
Heterocyclic Cations
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