Antisense oligodeoxynucleotides: Internalization, compartmentalization and non-sequence specificity

1996 ◽  
Vol 4 (1) ◽  
pp. 41-50 ◽  
Author(s):  
C. A. Stein ◽  
Ramaswamy Narayanan
Keyword(s):  
Antisense Oligodeoxynucleotides ◽  
Sequence Specificity

273: Knock-Down of BCL-2 By Antisense Oligodeoxynucleotides Induces Radiosensitization and Inhibition of Angiogenesis

2007 ◽  
Vol 177 (4S) ◽  
pp. 91-92
Author(s):  
Satoshi Anai ◽  
Yoshihisa Sakai ◽  
Steve Goodison ◽  
Kathleen Shiverick ◽  
Bob Brown ◽  
...  
Keyword(s):  
Antisense Oligodeoxynucleotides ◽  
Knock Down ◽  
Inhibition Of Angiogenesis

Neuroprotective effect of antisense oligodeoxynucleotides in experimental intracerebral hemorrhage in rats

2005 ◽  
Vol 25 (1_suppl) ◽  
pp. S505-S505
Author(s):  
Huijin Yan ◽  
Mengzhou Xue ◽  
Christopher Power ◽  
Marc R Del-Bigio ◽  
James Peeling
Keyword(s):  
Intracerebral Hemorrhage ◽  
Neuroprotective Effect ◽  
Antisense Oligodeoxynucleotides

Sequence Specificity Despite Intrinsic Disorder: How a Disease-Associated Val/Met Polymorphism Shifts Tertiary Interactions in a Long Disordered Protein

2019 ◽  
Author(s):  
Ruchi Lohia ◽  
Reza Salari ◽  
Grace Brannigan
Keyword(s):  
Secondary Structure ◽  
Electrostatic Interactions ◽  
Intrinsically Disordered Proteins ◽  
Disordered Proteins ◽  
Sequence Specificity ◽  
Intrinsically Disordered ◽  
Specific Effects ◽  
Heterogeneous Polymer ◽  
Non Local ◽  
Dynamics Simulations

<div>The role of electrostatic interactions and mutations that change charge states in intrinsically disordered proteins (IDPs) is well-established, but many disease-associated mutations in IDPs are charge-neutral. The Val66Met single nucleotide polymorphism (SNP) encodes a hydrophobic-to-hydrophobic mutation at the midpoint of the prodomain of precursor brain-derived neurotrophic factor (BDNF), one of the earliest SNPs to be associated with neuropsychiatric disorders, for which the underlying molecular mechanism is unknown. Here we report on over 250 μs of fully-atomistic, explicit solvent, temperature replica exchange molecular dynamics simulations of the 91 residue BDNF prodomain, for both the V66 and M66 sequence.</div><div>The simulations were able to correctly reproduce the location of both local and non-local secondary changes due to the Val66Met mutation when compared with NMR spectroscopy. We find that the local structure change is mediated via entropic and sequence specific effects. We show that the highly disordered prodomain can be meaningfully divided into domains based on sequence alone. Monte Carlo simulations of a self-excluding heterogeneous polymer, with monomers representing each domain, suggest the sequence would be effectively segmented by the long, highly disordered polyampholyte near the sequence midpoint. This is qualitatively consistent with observed interdomain contacts within the BDNF prodomain, although contacts between the two segments are enriched relative to the self-excluding polymer. The Val66Met mutation increases interactions across the boundary between the two segments, due in part to a specific Met-Met interaction with a Methionine in the other segment. This effect propagates to cause the non-local change in secondary structure around the second methionine, previously observed in NMR. The effect is not mediated simply via changes in inter-domain contacts but is also dependent on secondary structure formation around residue 66, indicating a mechanism for secondary structure coupling in disordered proteins. </div>

SYSTEMATIC IN VITRO EVALUATION OF SURVIVIN DIRECTED ANTISENSE OLIGODEOXYNUCLEOTIDES IN BLADDER CANCER CELLS

2004 ◽  
Vol 171 (6 Part 1) ◽  
pp. 2471-2476 ◽  
Author(s):  
SUSANNE FUESSEL ◽  
BERND KUEPPERS ◽  
SHUANGLI NING ◽  
MATTHIAS KOTZSCH ◽  
KAI KRAEMER ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Cells ◽  
Antisense Oligodeoxynucleotides ◽  
In Vitro Evaluation ◽  
Bladder Cancer Cells

scholarly journals Rely on Each Other: DNA Binding Cooperativity Shapes p53 Functions in Tumor Suppression and Cancer Therapy

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2422
Author(s):  
Oleg Timofeev ◽  
Thorsten Stiewe
Keyword(s):  
Cancer Therapy ◽  
Dna Binding ◽  
Cell Fate ◽  
Tumor Suppression ◽  
Quaternary Structure ◽  
Three Dimensional ◽  
Structural Basis ◽  
Sequence Specificity ◽  
Cell Fate Decisions ◽  
Cancer Mutations

p53 is a tumor suppressor that is mutated in half of all cancers. The high clinical relevance has made p53 a model transcription factor for delineating general mechanisms of transcriptional regulation. p53 forms tetramers that bind DNA in a highly cooperative manner. The DNA binding cooperativity of p53 has been studied by structural and molecular biologists as well as clinical oncologists. These experiments have revealed the structural basis for cooperative DNA binding and its impact on sequence specificity and target gene spectrum. Cooperativity was found to be critical for the control of p53-mediated cell fate decisions and tumor suppression. Importantly, an estimated number of 34,000 cancer patients per year world-wide have mutations of the amino acids mediating cooperativity, and knock-in mouse models have confirmed such mutations to be tumorigenic. While p53 cancer mutations are classically subdivided into “contact” and “structural” mutations, “cooperativity” mutations form a mechanistically distinct third class that affect the quaternary structure but leave DNA contacting residues and the three-dimensional folding of the DNA-binding domain intact. In this review we discuss the concept of DNA binding cooperativity and highlight the unique nature of cooperativity mutations and their clinical implications for cancer therapy.

scholarly journals Cis-Elements Governing Trinucleotide Repeat Instability in Saccharomyces cerevisiae

Genetics ◽  
2001 ◽  
Vol 157 (4) ◽  
pp. 1569-1579 ◽  
Author(s):  
Michael L Rolfsmeier ◽  
Michael J Dixon ◽  
Luis Pessoa-Brandão ◽  
Richard Pelletier ◽  
Juan José Miret ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Dna Repair ◽  
Sequence Analysis ◽  
Trinucleotide Repeat ◽  
Model Systems ◽  
Sequence Specificity ◽  
Cis Elements ◽  
Frequent Mutations ◽  
Yeast Genetic ◽  
Molecular Nature

Abstract Trinucleotide repeat (TNR) instability in humans is governed by unique cis-elements. One element is a threshold, or minimal repeat length, conferring frequent mutations. Since thresholds have not been directly demonstrated in model systems, their molecular nature remains uncertain. Another element is sequence specificity. Unstable TNR sequences are almost always CNG, whose hairpin-forming ability is thought to promote instability by inhibiting DNA repair. To understand these cis-elements further, TNR expansions and contractions were monitored by yeast genetic assays. A threshold of ∼15–17 repeats was observed for CTG expansions and contractions, indicating that thresholds function in organisms besides humans. Mutants lacking the flap endonuclease Rad27p showed little change in the expansion threshold, suggesting that this element is not altered by the presence or absence of flap processing. CNG or GNC sequences yielded frequent mutations, whereas A-T rich sequences were substantially more stable. This sequence analysis further supports a hairpin-mediated mechanism of TNR instability. Expansions and contractions occurred at comparable rates for CTG tract lengths between 15 and 25 repeats, indicating that expansions can comprise a significant fraction of mutations in yeast. These results indicate that several unique cis-elements of human TNR instability are functional in yeast.

scholarly journals Fine-Structure Mapping of Meiosis-Specific Double-Strand DNA Breaks at a Recombination Hotspot Associated With an Insertion of Telomeric Sequences Upstream of the HIS4 Locus in Yeast

Genetics ◽  
1996 ◽  
Vol 143 (3) ◽  
pp. 1115-1125 ◽  
Author(s):  
Fei Xu ◽  
Thomas D Petes
Keyword(s):  
Meiotic Recombination ◽  
Hydroxyl Groups ◽  
Sequence Specificity ◽  
Structure Mapping ◽  
Dna Breaks ◽  
Exonuclease Iii ◽  
Recombination Hotspot ◽  
Telomeric Sequences ◽  
Double Strand Dna Breaks ◽  
Double Strand Dna

Abstract Meiotic recombination in Saccharomyces cerevisiae is initiated by double-strand DNA breaks (DSBs). Using two approaches, we mapped the position of DSBs associated with a recombination hotspot created by insertion of telomeric sequences into the region upstream of HIS4. We found that the breaks have no obvious sequence specificity and localize to a region of ~50 bp adjacent to the telomeric insertion. By mapping the breaks and by studies of the exonuclease III sensitivity of the broken ends, we conclude that most of the broken DNA molecules have blunt ends with 3′-hydroxyl groups.

scholarly journals The DNA sequence specificity of stimulation of DNA polymerases by factor D.

1987 ◽  
Vol 262 (18) ◽  
pp. 8868-8874 ◽  
Author(s):  
M Fry ◽  
R Sharf ◽  
P Weisman-Shomer ◽  
P C Evers ◽  
L A Loeb
Keyword(s):  
Dna Sequence ◽  
Dna Polymerases ◽  
Sequence Specificity ◽  
Dna Sequence Specificity ◽  
Stimulation Of
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