What is a triplex DNA structure?
A DNA triplex is formed when pyrimidine or purine bases occupy the major groove of the DNA double Helix forming Hoogsteen pairs with purines of the Watson-Crick basepairs. Intermolecular triplexes are formed between triplex forming oligonucleotides (TFO) and target sequences on duplex DNA.
Is triple helix DNA possible?
Based on the way a double-stranded DNA helix is formed, a triple-stranded helix would not be possible. Because this happens to both single strands of the original double-stranded helix, you end up with two new double-stranded helices when you started with just one.
What was wrong with Linus Pauling’s DNA model?
This is Linus Pauling’s failed attempt to predict the structure of DNA. The problem with his triple helix model is that the phosphates form the helical core, with the bases pointing outwards. This would be impossible under normal cellular conditions.
Is the triple helix real?
DNA can form multi-stranded helices through either folding of one of the two strands or association of two, three, or four strands of DNA. In 1986, it was demonstrated that a short (15-mer) mixed-sequence triplex-forming oligonucleotide (TFO) formed a stable specific triple helical DNA complex [3].
Is triplex DNA pyrimidine rich?
While pyrimidine TFOs preferentially form triplexes with T–A duplex-rich TTS, purine TFOs form triplex structures with G–C-rich TTS. The complementary sequence recognition code of purine and pyrimidine TFOs increases the specificity and regulatory potential of TFO containing RNA molecules.
Is there a triple-stranded DNA?
Triple-stranded DNA (also known as H-DNA or Triplex-DNA) is a DNA structure in which three oligonucleotides wind around each other and form a triple helix.
What causes triple helix?
A triple helix is formed after the binding of a third strand to the major groove of a duplex DNA through Hoogsteen base pairing. Pyrimidine-rich and purine-rich sequences can form stable triplex structures as a consequence of the formation of A–T–A and C+–G–C triplets (Fig. 8.5).
What was the largest mistake with Linus Paulings model of DNA?
Though scientists proved Pauling and Corey’s model incorrect, “Nucleic Acids” helped scientists understand DNA’s structure and function as genetic material. In the early to mid-twentieth century, scientists investigated DNA’s structure using X-ray crystallography.
How do triplex drugs work?
The purine anti-parallel triplex motif utilizes TFOs made of A and G. They bind to the major groove of DNA in an anti-parallel sequence-specific manner by forming reverse Hoogsteen hydrogen bonds with the purine-rich target strand (3,60).
What is triplex forming oligonucleotides?
Definition. Triplex-forming oligonucleotides bind in the major groove of duplex DNA in a sequence-specific manner through the formation of hydrogen bonds. They can be used to inhibit the expression of particular genes.
How is the formation of triplex DNA stabilized?
There are two different types of intramolecular triplex DNA: H-DNA and H*-DNA. Formation of H-DNA is stabilized under acidic conditions and in the presence of divalent cations such as Mg2+. In this conformation, the homopyrimidine strand in the duplex bends back to bind to the purine strand in a parallel fashion.
How does a peptide nucleic acid form a triplex?
In peptide nucleic acid (PNA), the sugar-phosphate backbone of DNA is replaced with a protein-like backbone. PNAs form P-loops while interacting with duplex DNA, forming a triplex with one strand of DNA while displacing the other.
Can a supercoiled plasmid form a triplex?
Frank-Kamenetskii’s group later showed that a homopurine-homopyrimidine mirror repeat within a supercoiled plasmid was capable of forming an intramolecular triplex under low pH conditions ( 28, 29 ), implicating a physiological role for these complexes in gene regulation, as well as the cause of genome instability ( 30 ).
What are the problems with the triple helix model?
The problem with his triple helix model is that the phosphates form the helical core, with the bases pointing outwards. This would be impossible under normal cellular conditions.