User talk:EuniceB29/sandbox
There are two classes of triplex DNA: intermolecular and intramolecular formations. Intermolecular triplex DNA is formed when a triplex forming oligonucleotide (TFO) binds to the major groove of a duplex with purine and pyrimidine rich sequences. Intramolecular triplex DNA is formed from a duplex with homopurine and homopyrimidine (not sure what this means? A link to this wiki page would be nice, but someone can easily look it up if you don't want to insert a link Cantusn (talk) 13:12, 13 November 2017 (UTC)) strands with mirror repeat symmetry (1).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 bivalent cations (insert link) such as Mg2+. In this conformation, the homopyrimidine strand in the duplex bends back to bind to the purine strand in a parallel fashion. The base triads used to stabilize this conformation are T-A-*T and C-G*C+ (what does the little astrek and plus sign mean? Should I know this or is there going to be link to it?). Cantusn (talk) 13:12, 13 November 2017 (UTC) The cytosine in this base triad needs to be protonated in order to form this intramolecular triple helix, which is why this conformation is stabilized under acidic conditions and called H-DNA (5). H*-DNA has favorable formation conditions at neutral pH and in the presence of bivalent cations (4). This intramolecular conformation is formed from the binding of the homopurine and purine strand of the duplex in an antiparallel fashion. It is stabilized by T-A*A and C-G*G base triplets (5). (1). Supercoiling is a biologically relevant process because it occurs during replication of DNA (I don't think this sentence in necessary the next one is good and maybe just a link to what supercoiling is Cantusn (talk) 13:12, 13 November 2017 (UTC)). The level of supercoiling (insert link) in DNA influences the level of intramolecular triplex formation.
Triplex forming olignonucleotides (TFOs) are regions in intramolecular triplex DNA where triplex forming molecules, which are highly specific and bond to the major groove of double stranded DNA, bind and form a triplex structure. TFOs bind specifically to homopurine-homopyrimidine regions. TFOs can also cause triplexes to form, which can inhibit transcription by the means of actively competing with the binding of the transcription factor. Because of the high specificity of the triplex forming molecule, TFOs have been of interest in inhibiting transcription of genes. By using highly specific DNA segments to target TFO regions, expression of genes can be controlled (1). This application has novel implications in site-specific mutagenesis and gene therapy. The inhibition of transcription also has clinical application like its role in the recessive, autosomal gene for Frerick’s Ataxia (3). In Fredrick’s Ataxia, triplex DNA impairs the expression of a gene which results in the degeneration of the nervous system and spinal cord, impairing the movement of the limbs (2). (this is a really good paragraph, pretty easy to follow and gets to the point of one of the biological significance) Cantusn (talk) 13:12, 13 November 2017 (UTC) In addition to impairing or inhibiting transcription, triplexes have higher frequencies of double strand breaks, which can cause genomic rearrangements like insertions, translocations, inversions, and gross deletions. This genomic instability is a result of the triplex DNA supercoiling to overcome its highly unfavorable thermodynamic constraints. (triplex DNA supercoils and that causes the double strand breaks? There's nothing wrong with this I am just adding a note to ask you this in person to clarify'Italic text. Cantusn (talk) 13:12, 13 November 2017 (UTC) )
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[edit]-Intermolecular triplex refers to triplex formation between a duplex and a different strand of DNA. It can be a TFO, but could also be a neighboring chromosome.
-Remove: “and called H-DNA”
- “Supercoiling is a biologically relevant process because it occurs during replication of DNA”. I agree with User Cantusn, this sentence is not necessary.
--MichaelChiorazzo (talk) 15:47, 13 November 2017 (UTC)
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[edit]“The inhibition of transcription also has clinical application like its role in the recessive, autosomal gene for Frerick’s Ataxia.” This needs to be reworded a bit. Are TFO’s being researched to treat Frerick’s ataxia, or is triplex formation related to the onset of Frerick’s Ataxia.
--MichaelChiorazzo (talk) 15:48, 13 November 2017 (UTC)
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[edit]“This genomic instability is a result of the triplex DNA supercoiling to overcome its highly unfavorable thermodynamic constraints.” I don’t think this is necessary. You already mentioned the effect of supercoiling on triplex formation.