The triple helix: 50 years later, the outcome

Abstract

Triplex-forming oligonucleotides constitute an interesting DNA sequence-specific tool that can be used to target cleaving or cross-linking agents, transcription factors or nucleases to a chosen site on the DNA. They are not only used as biotechnological tools but also to induce modifications on DNA with the aim to control gene expression, such as by site-directed mutagenesis or DNA recombination. Here, we report the state of art of the triplex-based anti-gene strategy 50 years after the discovery of such a structure, and we show the importance of the actual applications and the main challenges that we still have ahead of us.

Fluorescent triplex-forming DNA oligonucleotides labeled with a thiazole orange dimer unit

“…1,2 Triplex formation for the DNA recognition has the remarkable advantage of not requiring strand opening of the target DNA duplex. TFOs have been used to recognize DNA in a living cell for the purposes such as regulation of transcription, 3 promotion of homologous recombination 4 and mutation of genomic DNA.…”

Triplexator: Detecting nucleic acid triple helices in genomic and transcriptomic data

“…Over the past decades, these rules have been scrutinized with respect to various determinants of triplex formation such as the chemistry of the nucleotides present in each strand (e.g., nucleotide backbone [Nielsen et al 1991;Roberts and Crothers 1992;Escude et al 1993;], sugars [Alam et al 2007], bases [Hogeland and Weller 1993], and modifications [Lee et al 1984]), the impact of pH (Sugimoto et al 2001), ionic environment (Wu et al 2002), sequence composition (Völker and Klump 1994), and base mismatches (Mergny et al 1991) using a multitude of complementary experimental setups (for more information, see the review Duca et al 2008). While each of the different determinants affects the triplex stability, these studies demonstrate that the rule set can be used to model triple-helix formation.…”

Chemical Modification of Oligonucleotides: A Novel Approach Towards Gene Targeting

“…In antigene technology, a single-stranded homopyrimidine triplex-forming oligonucleotide (TFO) added from outside may bind with homopurinehomopyrimidine stretch in target duplex DNA by Hoogsteen hydrogen bonding to form pyrimidine motif triplex, where T•A:T and C + •G:C base triplets are formed [3,4]. The formed triplex inhibits RNA polymerase and transcription factors-mediated transcription of target gene due to its steric hindrance, which may result in downregulation of expression level of target gene [3,4].…”