“…The antitumor agent, benzo[e]pyridoindole (BePI), has a higher affinity for triplex than for duplex DNA, and stabilizes H-DNA structures formed on plasmids inserted between the promoter and the coding sequence of the β-lactamase gene. The presence of BePI enhanced the H-DNA-induced transcription inhibition through the β-lactamase gene in E. coli cells, demonstrating the potential of small molecules as H-DNA modulators in cells [143].…”
Section: Stabilizing H-dnamentioning
confidence: 90%
“…There are many published reports that H-DNA can either up-regulate or down-regulate gene expression, depending on a number of factors, including the location of H-DNA in a gene, and the adjacent sequences and elements. In bacteria, when an H-DNA-forming sequence was inserted in a β-lactamase promoter, lacZ gene expression was increased significantly [140]; when an H-DNA structure was located at the coding region or between the promoter and coding sequence, a strong downregulation of gene transcription was observed [141][142][143].…”
Section: H-dna Is Implicated In Transcription Regulationmentioning
DNA structure is a critical element in determining its function. The DNA molecule is capable of adopting a variety of non-canonical structures, including three-stranded (i.e. triplex) structures, which will be the focus of this review. The ability to selectively modulate the activity of genes is a longstanding goal in molecular medicine. DNA triplex structures, either intermolecular triplexes formed by binding of an exogenously applied oligonucleotide to a target duplex sequence, or naturally occurring intramolecular triplexes (H-DNA) formed at endogenous mirror repeat sequences, present exploitable features that permit site-specific alteration of the genome. These structures can induce transcriptional repression and site-specific mutagenesis or recombination. Triplex-forming oligonucleotides (TFOs) can bind to duplex DNA in a sequence specific fashion with high affinity, and can be used to direct DNA-modifying agents to selected sequences. H-DNA plays important roles in vivo and is inherently mutagenic and recombinogenic, such that elements of the H-DNA structure may be pharmacologically exploitable. In this review we discuss the biological consequences and therapeutic potential of triple helical DNA structures. We anticipate that the information provided will stimulate further investigations aimed toward improving DNA triplexrelated gene targeting strategies for biotechnological and potential clinical applications.
“…The antitumor agent, benzo[e]pyridoindole (BePI), has a higher affinity for triplex than for duplex DNA, and stabilizes H-DNA structures formed on plasmids inserted between the promoter and the coding sequence of the β-lactamase gene. The presence of BePI enhanced the H-DNA-induced transcription inhibition through the β-lactamase gene in E. coli cells, demonstrating the potential of small molecules as H-DNA modulators in cells [143].…”
Section: Stabilizing H-dnamentioning
confidence: 90%
“…There are many published reports that H-DNA can either up-regulate or down-regulate gene expression, depending on a number of factors, including the location of H-DNA in a gene, and the adjacent sequences and elements. In bacteria, when an H-DNA-forming sequence was inserted in a β-lactamase promoter, lacZ gene expression was increased significantly [140]; when an H-DNA structure was located at the coding region or between the promoter and coding sequence, a strong downregulation of gene transcription was observed [141][142][143].…”
Section: H-dna Is Implicated In Transcription Regulationmentioning
DNA structure is a critical element in determining its function. The DNA molecule is capable of adopting a variety of non-canonical structures, including three-stranded (i.e. triplex) structures, which will be the focus of this review. The ability to selectively modulate the activity of genes is a longstanding goal in molecular medicine. DNA triplex structures, either intermolecular triplexes formed by binding of an exogenously applied oligonucleotide to a target duplex sequence, or naturally occurring intramolecular triplexes (H-DNA) formed at endogenous mirror repeat sequences, present exploitable features that permit site-specific alteration of the genome. These structures can induce transcriptional repression and site-specific mutagenesis or recombination. Triplex-forming oligonucleotides (TFOs) can bind to duplex DNA in a sequence specific fashion with high affinity, and can be used to direct DNA-modifying agents to selected sequences. H-DNA plays important roles in vivo and is inherently mutagenic and recombinogenic, such that elements of the H-DNA structure may be pharmacologically exploitable. In this review we discuss the biological consequences and therapeutic potential of triple helical DNA structures. We anticipate that the information provided will stimulate further investigations aimed toward improving DNA triplexrelated gene targeting strategies for biotechnological and potential clinical applications.
“…This plasmid is a pBR322 derivative, where a 55 bp oligopyrimidine †oligo-purine mirror repeat sequence was inserted between the bla promoter and the coding start site of the b-lactamase gene. 31 This insert was previously examined by chemical probing using chloracetaldehyde and shown to adopt an H-DNA conformation in supercoiled plasmid in vitro. 31 The parent pBR322, which has no H-DNA forming sequence, was used as a control.…”
Section: Effect Of H-dna Forming Sequences On Downstream Gene Expressmentioning
confidence: 99%
“…31 This insert was previously examined by chemical probing using chloracetaldehyde and shown to adopt an H-DNA conformation in supercoiled plasmid in vitro. 31 The parent pBR322, which has no H-DNA forming sequence, was used as a control. Increasing concentrations of BQQ were added to E. coli cultures carrying pBR322 or pIbla69, and growth was monitored by measuring absorbance.…”
Section: Effect Of H-dna Forming Sequences On Downstream Gene Expressmentioning
“…To date, only one study has addressed the question of the effect of triplex-binding ligands on intramolecular triple helices [146]. A mirror repeat sequence was inserted between the E. coli b-lactamase gene, which confers resistance to the antibiotic ampicillin, and its promoter in a plasmid, which also expresses the resistance gene for the antibiotic tetracycline.…”
Section: Binding To Intramolecular Triple Helicesmentioning
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