A similar triple C. C base pair is not stable unless the second C is protonated thus forming a C. Thus far, it has been shown that the formation of a stable triplex helix of the Py. Py type is relatively straightforward. It remains a challenge, however, to design oligonucleotides that can bind to a specific DNA duplex using all four bases.
Triple Helix, Nucleic Acids (Molecular Biology)
Triple Resonance Molecular Biology. Loss of FANCJ has been described in several cancers but especially associated with breast carcinomas. However, it should be noted that while all of these helicases can act upon triplex structures, they can also act upon other non-B structures e.
G-quadruplex, cruciform, slipped-strands as well as normal duplex nucleic acids [ 42 ]. This has been more difficult to establish for triplex-binding proteins. For example, while the human Orc4 protein plays an essential role in the initiation of replication and has been found to preferentially bind pyrimidine motif triplex DNA, overexpression of this protein has not been strongly implicated in any cancer [ 24 , 43 ].
Triplexator: Detecting nucleic acid triple helices in genomic and transcriptomic data
Certain high mobility group proteins e. HMGB1 have been reported to promote the formation of purine motif triplexes [ 26 ]. However, they are well known to interact with other nucleic acid structures, preferentially single-stranded DNA, and have paradoxical oncogenic and tumour suppressive roles in several cancers [ 44 , 45 ]. Finally, while RPA preferentially directs XPA to DNA damage proximal to triplexes and facilitates repair, overexpression of RPA adversely impacts homologous recombination and elevated genomic instability, suggesting that the aforementioned repair does not reduce the incidence of certain cancers [ 46 ].
The best evidence for a relationship between triplex-binding proteins and cancer can be found in the recent work of Nelson et al. However, similar correlations were not observed for other triplex species observed in these extracts.
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Using affinity chromatography, nano-scale high-performance liquid chromatography and electrospray ionisation tandem mass spectrometry, they were able to identify three proteins specifically bound to their purine motif triplex DNA probe: U2AF65 is also a known RNA polymerase II-associated splicing factor, involved in the recognition of degenerate pyrimidine tracts downstream of the branch point during spliceosome assembly. Of the 63 patient samples 51 were then investigated by western blotting.
Similar correlations could not be made with either PSF or P54nrb. Curiously, western blotting indicated a strong correlation between H3 levels and the DNA helicase WRN, suggesting coordinate regulation of triplex-stabilising and triplex-destabilising activities. This remains an open question at this time. Multiple lines of evidence suggesting the existence of triplex nucleic acids in vivo do exist. However, they are far from conclusive.
Triple helix-interacting proteins and cancer
Fundamental knowledge as to the exact types of triplex present: DNA, RNA or hybrid, pyrimidine motif or purine motif, intramolecular or intermolecular, as yet remains unanswered. Once a better understanding of triplex physiology has been achieved, then studies such as those of Nelson et al. Note that further studies of triplex-interacting proteins, both stabilising and destabilising, are still potentially worthwhile. However, regardless of the observed strength of correlations found, studies with these proteins cannot be considered conclusive proof for a role of triplexes in cancer.
To date for the limited number of triplex-interacting proteins identified, all have additional described biological roles beyond those involving triplex structures. Similarly, the described triplex-binding proteins are also known to avidly bind a variety of nucleic acid structures, ranging from single strands to branched nucleic acids. Thus, the identification of proteins that specifically and exclusively recognise triplex structures is paramount.
In conclusion, more studies will be needed before the full potential of triplex nucleic acids and their role in cancer can be realised. All authors contributed to the conception, design, and preparation of the manuscript, as well as read and approved the final manuscript. Watson-Crick hydrogen bonding, 3 third strand of triplex, Pu purine-rich strand of duplex, Py pyrimidine-rich strand of duplex.
Multiple stabilities indicate values observed for different triplex sequences. First value is dominant among three independent investigations 8 , 9 , Triple helix-interacting proteins and cancer. OA Molecular Oncology Apr 01;1 1: It pays particular attention to the different methods for investigating these molecules, a feature which will be welcomed by those new to the field.
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- Triple-stranded DNA.
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Dervan peptide nucleic acid plasmid poly dT poly U polyamines polynucleotide Proc promoter protein protonated psoralen purine purine strand PyPu tracts PyPuPy triplex pyrimidine pyrimidine strand regions Reprinted with permission RNA polymerase single-stranded Soyfer specific spermine studies supercoiling superhelical target third strand thymine topoisomers transcription transition triads triple helix formation triple-stranded complexes triplex formation triplex stabilization triplex structure triplex-forming oligonucleotides vitro Wang.
Sequencing end-labeled DNA with base-specific chemical cleavages. Applications of Kinetic Modelling G.