Jump to content

User:Scalvert2000/H-DNA

From Wikipedia, the free encyclopedia

Structures

[edit]
Base triads of H-DNA triplexes: CG*G, TA*A, TA*T, an CG*A+.

Intermolecular and intramolecular formations[edit]

[edit]

*****There are two classes of triplex DNA: intermolecular and intramolecular formations. An intermolecular triplex refers to triplex formation between a duplex and a different (third) strand of DNA. The third strand can either be from a neighboring chromosome or a triplex forming oligonucleotide (TFO). Intramolecular triplex DNA is formed from a duplex with homopurine and homopyrimidine strands with mirror repeat symmetry. The degree of supercoiling in DNA influences the amount of intramolecular triplex formation that occurs. 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. The base triads used to stabilize this conformation are T-A*T and C-G*C+. The cytosine of 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. H*-DNA has favorable formation conditions at neutral pH and in the presence of divalent cations. 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.*** Text from wikipedia page inserted to give relevance to the image.

Biological Implications of H-DNA

[edit]

Genetic Instability

[edit]

Considerable research has been funneled into the biological implications relating to the presence of H-DNA in the major breakpoint regions (Mbr) and double-strand-breakpoints of certain genes. Recent work has linked the presence of non-B-DNA structures with cases of genetic instability.[1]

Polypurine mirror-repeat H-DNA forming sequences were found neighboring the P1 promoter of the c-MYC gene and are associated with the major breakpoint hotspots of this region. Cases of genetic instability were also observed in the F1 offspring of transgenic mice after incorporation of human H-DNA-forming sequences paired with Z-DNA sequences into their genomes where no instability was previously reported.[2] Additionally, formation of R.R.Y. triplex conformations have been observed at the Mbr of the bcl-2 gene. Formation of these structures has been posited to cause the t(14;18) translocation observed in many cancers and most follicular lymphomas. This observation has led to research that indicated a substantial decrease in translocation events can be observed after blocking the formation of H-DNA by altering the sequence of this region slightly.[2][3] Long tracts of GAA·TTC have also been observed to form very stable triplex structures. Interactions between these two triplex structures, termed sticky DNA, has been shown to interrupt transcription of the X25, or frataxin gene. As decreased levels of the protein frataxin is associated with Friedreich's ataxia, formation of this instability has been suggested to be the basis for this genetic disease.[4][5]

Additionally, DNA damage can lead to mutations that disrupt critical cellular processes like DNA replication and transcription. The importance of these processes for survival has led to the development of complex DNA repair mechanisms that allow cells to recognize and fix DNA damage. Non-canonical DNA structures are perceived as damage by the cell, and recent work has shown an increased prevalence of mutations near non-B-DNA-forming sequences. Some of these mutations are due to the interactions between H-DNA and the enzymes involved in DNA replication and transcription, where H-DNA interferes with these processes and triggers various DNA repair mechanisms. This can cause genetic instability and implicates H-DNA in cancer formation.[6]

DNA Replication

[edit]

DNA replication has been shown to affect the function of various DNA repair enzymes. H-DNA formation involves the formation of single-stranded DNA (ssDNA), which is more susceptible to attack by nucleases.[6] Various nucleases have been shown to interact with H-DNA in a replication-dependent and replication-independent manner.[6]

A study using human cells found that the nucleotide excision repair (NER) nucleases ERCC1-XPF and ERCC1-XPG induced genetic instability.[7] These enzymes cleave H-DNA at the loop formed by the two Hoogsteen hydrogen-bonded strands and the 5' end of the other Watson-Crick hydrogen-bonded strand, respectively.[7] This cleavage has been shown to induce large deletions that cause double strand breaks (DSBs) in DNA that can lead to genetic instability.[6][7] In cells deficient in ERCC1-XPF and ERCC1-XPG, these deletions were less prevalent near H-DNA forming sequences.[7] Additionally, more mutations were found in ERCC1-XPF and ERCC1-XPG deficient cells in the absence of DNA replication, which suggests they process H-DNA in a replication-independent manner.[7]

Alternatively, the DNA-replication repair nuclease FEN1 was found to suppress genetic instability.[7] Similar to ERCC1-XPG, FEN1 cleaves H-DNA at the 5' end of the strand not involved in Hoogsteen hydrogen-bonding.[7] HeLa cells deficient in FEN1 showed higher prevalence of deletions near H-DNA forming sequences, but H-DNA induced mutagenesis was more pronounced in FEN1 deficient cells in the presence of DNA replication.[7] This suggests FEN1 suppresses H-DNA-induced mutagenesis in a replication-dependent manner.[7]

H-DNA has been implicated in human cancer etiology because of the prevalence of triplex-forming sequences near translocation breakpoints in cancer genomes.[7] Replication-mediated nuclease activity with H-DNA highlights another way H-DNA-induced mutagenesis and lead to cancer growth.

Transcription

[edit]

H-DNA forming sequences can also cause genetic instability by interfering with and stopping transcription prematurely.[6] The DNA unwinding involved in transcription makes it more susceptible to damage. In transcription-coupled repair (TCR), a lesion on the template strand of DNA stops the function of RNA polymerase and signals TCR factors to resolve the damage by excising it.[8] H-DNA can be perceived as one of these lesions.

A study observing transcription by T7 RNA polymerase on a stable H-DNA forming sequence analog found transcription blockage at the duplex-to-triplex junction. Here, the template strand was the central strand of the triplex, and the difficulty of disrupting its Watson-Crick and Hoogsteen hydrogen bonds stopped transcription from progressing.[9]

When transcription by T7 was observed on the P0 promoter of the c-MYC gene, the shortened transcription products that were found indicated that transcription was stopped in close proximity to the H-DNA forming sequence downstream of the promoter. Formation of the triplex in this region prevents T7 from traveling down the template strand because of the steric hindrance it causes. This stops transcription and signals for TCR factors to come resolve the triplex, which results in DNA excision that can cause genetic instability.[8] The mirror symmetry and prevalence of guanine residues in the c-MYC gene gives it a high propensity for non-canonical DNA structure formation.[10] This coupled with the activity of TCR factors during transcription makes it highly mutagenic, with it playing a role in the development of Burkitt lymphoma and leukemia.[8][10]

H-DNA in complex with a peptide nucleic acid (PNA). PDB ID: 1PNN

Applications of Triplex forming Oligonucleotides:

[edit]

The triple-stranded DNA regions can be generated through the association of Triplex Forming Oligonucleotides (TFO) and Peptide Nucleic Acids (PNAs). Historically, TFO binding has been shown to inhibit transcription, replication, and protein binding to DNA[11]. TFOs tethered to mutagens have also been shown to promote DNA damage and induce mutagenesis. Although TFO have been known to hinder transcription and replication of DNA, recent studies have shown that TFO can be utilized to mediate site specific gene modifications both in vitro and in vivo. Another recent study has also shown that TFOs can be used for suppression of oncogenes and proto-oncogenes to reduce cancer cell growth. For example, a recent study has used TFOs to reduce cellular death in hepatoma cells through the decreasing the expression of MET.

PNA TFOs have the ability to enhance recombination frequencies, leading to targeted, specific editing of genes. The PNA-DNA-PNA triplex helix is able to be recognized by the cell’s own DNA repair mechanism, which sensitizes the surrounding DNA for homologous recombination. In order for a site-specific PNA structure to mediate recombination within a DNA sequence,  a bis-PNA structure can be coupled with a 40nt DNA fragment that is homologous to an adjacent region on the target gene[12]. The linking of a TFO to a donor DNA strand has been shown to induce recombination of the targeted gene and the adjacent gene target region. The mechanism for this form of recombination and repair have been linked to the nucleotide excision repair (NER) pathway playing a role in recognizing and repairing triplex structures[12][11]. Multiple investigations suggests that the xeroderma pigmentosum group A (XPA) and replication protein A (RPA), which are NER factors, are able to bind specifically as a complex to cross-linked triplex structures. It is known that this mechanism alongside others play a role in recognizing and repairing triplex structures.

The in vivo delivery of TFOs has been a major barrier in using TFOs for gene modification. One study on in vivo targeting of hematopoietic stem cells proposed a novel technique of conjugating PNA molecules with cell penetrating peptide (CPPs) alongside poly(lactic-co-glycolic acid) (PLGA) nanoparticles to enable 6 bp modifications in the CCR5 gene[13]. The editing of the CCR5 gene has been linked to HIV-1 resistance[14]. CPPs are proteins that are able to carry “cargo” such as small proteins or molecules successfully into cells. The PGLAs are biodegradable material that encapsulate PNA molecules as nanoparticles for site specific genome modifications [13]. The study found that the PNA-DNA PGLA nanoparticles were able to effectively edit the hematopoietic stem cells with lower toxicity and virus-free and the conjugation with CPP offered direct targeting of the genes for site-specific mutagenesis in the stem cells.

In a novel study of cystic fibrosis (CF) gene therapy, three tail-clamp peptide nucleic acids (PNAs) alongside donor DNA molecule were engineered to be delivered by nanoparticles to correct F508 del mutations on the cystic fibrosis transmembrane conductance regulator (CFTR) in human bronchial epithelial cells in vivo and in vitro[15]. The F508 del mutation is the most commonly occurring mutation which leads a person to have CF[16]. The F508 mutation leads to a loss of function of the CFTR, which is a plasma membrane chloride channel that is regulated by a cyclic-adenosine monophosphate(cAMP). In this study, they were able to create the novel treatment approach for CF through the use of nanoparticles to correct the F508 del CFTR mutation both in vitro in human bronchial epithelial (HBE) cells and in vivo in a CF mouse model which resulted in the appearance of CFTR-dependent chloride transport[15].

Triplex Forming Oligonucleotides (TFO)[edit]

[edit]

Peptide Nucleic Acids (PNA)

Peptide Nucleic acids are synthetic oligonucleotides that resist protease degradation and are used to induce repair at site specific triplex formation regions on DNA genomic sites. PNAs are able to bind with high affinity and sequence specificity to a complementary  DNA sequence through Watson-Crick base pairing binding and are able to form triple helices through parallel orientation Hoogsteen bonds with the PNA facing the 5’-end of the DNA strand[17]. The PNA-DNA triplex are stable because PNAs are comprised of a neutrally charged pseudopeptide backbone which binds to bind to the double stranded DNA (dsDNA) sequence [18]. Similar to homopyrimidine in TFOs, homopyrimidine in PNAs are able to form a bond with the complementary homopurine in target sequence of the dsDNA. These DNA analogues are able to bind to dsDNA by exploiting ambient DNA conditions and different predicting modes of recognition. This is different from TFOs which bind though the major groove recognition of the dsDNA.

One of the predicting modes of recognition used for recognition is through a duplex invasion. Within mixed A–T/G–C dsDNA sequence is targeted by a pair of pseudo-complementary (pc) PNAs which are able to bind to dsDNAs via double invasion through the simultaneous formation of diaminopurine (D) and thiouracil (Us) which substitute for adenine and thymine, respectively. The pc PNA pair form a D-T and Us -A and G-C or C-G Watson-Crick paired PNA-DNA helix with each of complementary DNA strands. Another form of recognized duplex invasion at targeted sequence can occur in dsDNA containing mixed T–C sequences[12]. This form of duplex invasion is achieved through a complimentary sequence of homopurine PNA oligomers. This triplex is formed from a PNA-DNA hybrid that binds anti-parallel with the complementary DNA sequence and results in a displaced non-complimentary DNA strand[18].

Additionally, PNA can be modified to form “clamp” triplex structures at the target site . One type of “clamp” formed is a bis -PNA structure, in which two PNA molecules are held together by a flexible linker such as 8-amino-3,6-dioxaoctanoic acid (O)[19]. The bis-PNA structure forms a PNA-DNA-PNA triplex at the target site, where one strand forms Watson-Crick base pairs with DNA in an antiparallel orientation and the other strand forms Hoogsteen base pairs with the homopurine DNA strand in the DNA-PNA duplex[12]. A tail clamp PNA (tcPNA) is also another form of triplex clamp that can also be formed. TcPNAs contain an extended 5-10 bp tail that forms a PNA/DNA duplex in addition to a PNA-DNA-PNA “clamp”. This allows for more specified PNA binding without the need for a homopyrimidie/pyridine stretch[18]. These clamp structures had been shown to have high affinity and specificity. The addition of lysine residues to either or both ends of PNA’s could be used to increase cellular uptake and binding.

Gene Regulation[edit] (L.R)

[edit]

According to several published articles, H-DNA has the ability to regulate gene expression depending on factors such as location and sequences in proximity. Although intergenic regions of the prokaryotic genome have shown low traces of naturally occurring H-DNA or triplex motifs, H-DNA structures have shown to be more prevalent in the eukaryotic genome. H-DNA has been show to be especially abundant in mammalian cells including humans (1 in every 50,000 bp)[20]. Genetic sequences involved in gene regulation are typically found in the promoter regions of the eukaryotic genome[20].

Consequently, the promoter region has displayed the ability to form H-DNA with a higher frequency[20]. A bioinformatic analysis of the S. cerevisiae genome observed the occurrence of H-DNA and other triplate DNA motifs in four organizational regions: introns, exons, promoter regions and miscellaneous regions. The bioinformatic displayed a total of 148 H-DNA or triplet DNA possible structures. The promoter region accounted for the higher frequency with 71 triplate structures, while the exons accounted for 57 triplate structures and the introns and miscellaneous accounted for 2 and 18 structures [21].

In vitro and in vivo studies of eukaryotic genome expression resulted in one of three results: up regulation, down regulation, or no change in the presence of H-DNA motifs[20]. Kato et. al. reported upregulation expression of lacZ, when H-DNA was introduced to the B-lactamase promoter[22][20]. On the other hand, a similar study (Brachmachari et al.) reported no statistically significant inhibition of the lacZ reporter gene when H-DNA was inserted into the genome of mammalian COS cells[20]. Although studies suggest regulation of H-DNA, the mechanism is still under investigation. Potaman et al. associates the mechanism of gene regulation to the interactions between the H-DNA and the TATA box found in the promoter region of Na,K-ATPase. In H-DNA formations adjacent to a TATA box, the H-DNA structure destabilizes the T-A bonds essential for transcription. The interference with the TATA box inhibits the transcriptional machinery and transcription initiation which interferes with gene expression[20][23]. Other mechanisms associated with the genomic expression of a genetic sequence in the presence of H-DNA involves TFOs. In vitro studies have highlighted a decrease in gene expression in the presence of TFOs in mammalian cells[24]. Another possible mechanism presented by Valentina et al. suggest the 13-mer AG motif oligonucleotide triplex complex (TFO complex) downregulates the transcription of mRNA through competitive inhibition[25]. Direct inhibition of gene expression from H-DNA is key to mutagenesis, replication inhibition, and even DNA recombination in the genome[20].

Crystal Structure of RecA-DNA and D-Loop Formaton, PDB:7JY7

Recombination

[edit]
H-DNA Structure of RecA PDB: 7JY7

H-DNA motifs have been shown to stimulate homologous recombination with different mechanisms. Initial implications for the role of H-DNA in recombination came in the early 1990s when observing RecA, a bacterial DNA recombination protein composed of triple-helix DNA. RecA exhibits enzymatic activity essential for recombination[26][27]. Homologous recombination involving H-DNA motifs have also been found in eukaryotes. RadA, a homologous protein to RecA, has been shown to have the same enzymatic activity in recombination as RecA[28].The protein has the ability to promote homologous strand exchange through parallel triple stranded helices[29][30]. The single stranded DNA (ssDNA) and complementary double stranded DNA (dsDNA) will form a D-loop structure[31][20]. Another possible mechanism for RecA involves the ssDNA from two separate H-DNA structures to form Watson-Crick base pairs. The new structure is known as a Holliday junction, an intermediate in homologous recombination[20]. H-DNA is also found in other forms of recombination. In mammalian cells, H-DNA-sequences displayed a high frequency of recombination. For example, a study conducted on myeloma cell line of mice found H-DNA structures in Cγ2a and Cγ2b, which participate in sister chromatid exchange[20].

History

[edit]

An alternative triple-stranded DNA structure was described in 1957[32]. Felsenfeld, Davies, and Rich predicted that if one strand contained only purines and the other strand only purines, the strand would undergo a conformational change to form a triple stranded DNA helix. The triple-stranded DNA (H-DNA) was predicted to be composed of one polypurine and two polypyrimidine strands[26][32]. It was thought to occur in only one in vivo biological process: as an intermediate product during the action of the E. coli recombination enzyme RecA.[32]. Early models in the 1960s predicted the formation of complexes between polycetiylic and guanine oligonucleotides. The models suggested interactions known as Hogsten pairing (non-Watson-Crick interactions) located in the major groove[26]. Shortly after, triple helices composed of one pyrimidine and two purine strands were predicted[26].The discovery of in H-DNA stretches in supercoiled plasmids peaked modern interest in the potential function of triplex structures in living cells[33]. Additionally, it was soon found that homopyrimidine and some purine-rich oligonucleotide are able form a stable H-DNA structure with the  homopurine-homopyrimidine binding sequence-specific structures on the DNA duplexes[34].

  1. ^ McKinney, Jennifer A.; Wang, Guliang; Mukherjee, Anirban; Christensen, Laura; Subramanian, Sai H. Sankara; Zhao, Junhua; Vasquez, Karen M. (2020-01-13). "Distinct DNA repair pathways cause genomic instability at alternative DNA structures". Nature Communications. 11 (1): 236. doi:10.1038/s41467-019-13878-9. ISSN 2041-1723. PMC 6957503. PMID 31932649.{{cite journal}}: CS1 maint: PMC format (link)
  2. ^ a b Wang G, Vasquez KM (July 2014). "Impact of alternative DNA structures on DNA damage, DNA repair, and genetic instability". DNA Repair. 19: 143–51. doi:10.1016/j.dnarep.2014.03.017. PMC 4216180. PMID 24767258.
  3. ^ Raghavan SC, Chastain P, Lee JS, Hegde BG, Houston S, Langen R, Hsieh CL, Haworth IS, Lieber MR (June 2005). "Evidence for a triplex DNA conformation at the bcl-2 major breakpoint region of the t(14;18) translocation". The Journal of Biological Chemistry. 280 (24): 22749–60. doi:10.1074/jbc.M502952200. PMID 15840562.
  4. ^ Wang G, Vasquez KM (September 2004). "Naturally occurring H-DNA-forming sequences are mutagenic in mammalian cells". Proceedings of the National Academy of Sciences of the United States of America. 101 (37): 13448–53. doi:10.1073/pnas.0405116101. PMC 518777. PMID 15342911.
  5. ^ Vetcher AA, Napierala M, Iyer RR, Chastain PD, Griffith JD, Wells RD (October 2002). "Sticky DNA, a long GAA.GAA.TTC triplex that is formed intramolecularly, in the sequence of intron 1 of the frataxin gene". The Journal of Biological Chemistry. 277 (42): 39217–27. doi:10.1074/jbc.M205209200. PMID 12161437.
  6. ^ a b c d e Wang, Guliang; Vasquez, Karen (2017-01-05). "Effects of Replication and Transcription on DNA Structure-Related Genetic Instability". Genes. 8 (1): 17. doi:10.3390/genes8010017. ISSN 2073-4425. PMC 5295012. PMID 28067787.{{cite journal}}: CS1 maint: PMC format (link) CS1 maint: unflagged free DOI (link)
  7. ^ a b c d e f g h i j Zhao, Junhua; Wang, Guliang; del Mundo, Imee M.; McKinney, Jennifer A.; Lu, Xiuli; Bacolla, Albino; Boulware, Stephen B.; Zhang, Changsheng; Zhang, Haihua; Ren, Pengyu; Freudenreich, Catherine H. (2018-01-30). "Distinct Mechanisms of Nuclease-Directed DNA-Structure-Induced Genetic Instability in Cancer Genomes". Cell Reports. 22 (5): 1200–1210. doi:10.1016/j.celrep.2018.01.014. PMC 6011834. PMID 29386108.{{cite journal}}: CS1 maint: PMC format (link)
  8. ^ a b c Belotserkovskii, Boris P.; De Silva, Erandi; Tornaletti, Silvia; Wang, Guliang; Vasquez, Karen M.; Hanawalt, Philip C. (2007-11-02). "A Triplex-forming Sequence from the Human c- MYC Promoter Interferes with DNA Transcription". Journal of Biological Chemistry. 282 (44): 32433–32441. doi:10.1074/jbc.M704618200. ISSN 0021-9258.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  9. ^ Pandey, Shristi; Ogloblina, Anna M.; Belotserkovskii, Boris P.; Dolinnaya, Nina G.; Yakubovskaya, Marianna G.; Mirkin, Sergei M.; Hanawalt, Philip C. (2015-08-18). "Transcription blockage by stable H-DNA analogs in vitro". Nucleic Acids Research. 43 (14): 6994–7004. doi:10.1093/nar/gkv622. ISSN 0305-1048. PMC 4538819. PMID 26101261.{{cite journal}}: CS1 maint: PMC format (link)
  10. ^ a b del Mundo, Imee Marie A.; Zewail-Foote, Maha; Kerwin, Sean M.; Vasquez, Karen M. (2017-05-05). "Alternative DNA structure formation in the mutagenic human c-MYC promoter". Nucleic Acids Research. 45 (8): 4929–4943. doi:10.1093/nar/gkx100. ISSN 0305-1048. PMC 5416782. PMID 28334873.{{cite journal}}: CS1 maint: PMC format (link)
  11. ^ a b Ricciardi, Adele S.; McNeer, Nicole A.; Anandalingam, Kavitha K.; Saltzman, W. Mark; Glazer, Peter M. (2014), Wajapeyee, Narendra (ed.), "Targeted Genome Modification via Triple Helix Formation", Cancer Genomics and Proteomics, vol. 1176, New York, NY: Springer New York, pp. 89–106, doi:10.1007/978-1-4939-0992-6_8, ISBN 978-1-4939-0991-9, PMC 5111905, PMID 25030921, retrieved 2020-12-15{{citation}}: CS1 maint: PMC format (link)
  12. ^ a b c d Rogers, Faye A.; Vasquez, Karen M.; Egholm, Michael; Glazer, Peter M. (2002-12-24). "Site-directed recombination via bifunctional PNA–DNA conjugates". Proceedings of the National Academy of Sciences. 99 (26): 16695–16700. doi:10.1073/pnas.262556899. ISSN 0027-8424. PMC 139206. PMID 12461167.{{cite journal}}: CS1 maint: PMC format (link)
  13. ^ a b McNeer, N A; Schleifman, E B; Cuthbert, A; Brehm, M; Jackson, A; Cheng, C; Anandalingam, K; Kumar, P; Shultz, L D; Greiner, D L; Mark Saltzman, W (2013-06). "Systemic delivery of triplex-forming PNA and donor DNA by nanoparticles mediates site-specific genome editing of human hematopoietic cells in vivo". Gene Therapy. 20 (6): 658–669. doi:10.1038/gt.2012.82. ISSN 0969-7128. PMC 3713483. PMID 23076379. {{cite journal}}: Check date values in: |date= (help)CS1 maint: PMC format (link)
  14. ^ Schleifman, Erica B.; Bindra, Ranjit; Leif, Jean; del Campo, Jacob; Rogers, Faye A.; Uchil, Pradeep; Kutsch, Olaf; Shultz, Leonard D.; Kumar, Priti; Greiner, Dale L.; Glazer, Peter M. (2011-09). "Targeted Disruption of the CCR5 Gene in Human Hematopoietic Stem Cells Stimulated by Peptide Nucleic Acids". Chemistry & Biology. 18 (9): 1189–1198. doi:10.1016/j.chembiol.2011.07.010. PMC 3183429. PMID 21944757. {{cite journal}}: Check date values in: |date= (help); no-break space character in |first10= at position 5 (help); no-break space character in |first11= at position 6 (help); no-break space character in |first5= at position 5 (help); no-break space character in |first8= at position 8 (help); no-break space character in |first= at position 6 (help); no-break space character in |last4= at position 4 (help)CS1 maint: PMC format (link)
  15. ^ a b McNeer, Nicole Ali; Anandalingam, Kavitha; Fields, Rachel J.; Caputo, Christina; Kopic, Sascha; Gupta, Anisha; Quijano, Elias; Polikoff, Lee; Kong, Yong; Bahal, Raman; Geibel, John P. (2015-04-27). "Nanoparticles that deliver triplex-forming peptide nucleic acid molecules correct F508del CFTR in airway epithelium". Nature Communications. 6 (1): 6952. doi:10.1038/ncomms7952. ISSN 2041-1723. PMC 4480796. PMID 25914116.{{cite journal}}: CS1 maint: PMC format (link)
  16. ^ Lukacs, Gergely L.; Verkman, A.S. (2012-02). "CFTR: folding, misfolding and correcting the ΔF508 conformational defect". Trends in Molecular Medicine. 18 (2): 81–91. doi:10.1016/j.molmed.2011.10.003. PMC 3643519. PMID 22138491. {{cite journal}}: Check date values in: |date= (help)CS1 maint: PMC format (link)
  17. ^ Jain, Aklank; Wang, Guliang; Vasquez, Karen M. (2008-08). "DNA triple helices: Biological consequences and therapeutic potential". Biochimie. 90 (8): 1117–1130. doi:10.1016/j.biochi.2008.02.011. PMC 2586808. PMID 18331847. {{cite journal}}: Check date values in: |date= (help)CS1 maint: PMC format (link)
  18. ^ a b c Hansen, Mads E.; Bentin, Thomas; Nielsen, Peter E. (2009-07-01). "High-affinity triplex targeting of double stranded DNA using chemically modified peptide nucleic acid oligomers". Nucleic Acids Research. 37 (13): 4498–4507. doi:10.1093/nar/gkp437. ISSN 0305-1048. PMC 2715256. PMID 19474349.{{cite journal}}: CS1 maint: PMC format (link)
  19. ^ Montazersaheb, Soheila; Hejazi, Mohammad Saeid; Nozad Charoudeh, Hojjatollah (2018-11-29). "Potential of Peptide Nucleic Acids in Future Therapeutic Applications". Advanced Pharmaceutical Bulletin. 8 (4): 551–563. doi:10.15171/apb.2018.064. ISSN 2228-5881. PMC 6311635. PMID 30607328.{{cite journal}}: CS1 maint: PMC format (link)
  20. ^ a b c d e f g h i j k Jain, Aklank; Wang, Guliang; Vasquez, Karen M. (2008-8). "DNA Triple Helices: biological consequences and therapeutic potential". Biochimie. 90 (8): 1117–1130. doi:10.1016/j.biochi.2008.02.011. ISSN 0300-9084. PMC 2586808. PMID 18331847. {{cite journal}}: Check date values in: |date= (help)
  21. ^ Zain, R.; Sun, J-S (2003-05-01). "Do natural DNA triple-helical structures occur and function in vivo?". Cellular and Molecular Life Sciences CMLS. 60 (5): 862–870. doi:10.1007/s00018-003-3046-3. ISSN 1420-9071.
  22. ^ Kato, M.; Shimizu, N. (1992-10). "Effect of the potential triplex DNA region on the in vitro expression of bacterial beta-lactamase gene in superhelical recombinant plasmids". Journal of Biochemistry. 112 (4): 492–494. doi:10.1093/oxfordjournals.jbchem.a123927. ISSN 0021-924X. PMID 1491004. {{cite journal}}: Check date values in: |date= (help)
  23. ^ Potaman, Vladimir N.; Ussery, David W.; Sinden, Richard R. (1996-06-07). "Formation of a Combined H-DNA/Open TATA Box Structure in the Promoter Sequence of the Human Na,K-ATPase α2 Gene". Journal of Biological Chemistry. 271 (23): 13441–13447. doi:10.1074/jbc.271.23.13441. ISSN 0021-9258.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  24. ^ Seidman, Michael M.; Glazer, Peter M. (2003-08-15). "The potential for gene repair via triple helix formation". The Journal of Clinical Investigation. 112 (4): 487–494. doi:10.1172/JCI19552. ISSN 0021-9738. PMC 171401. PMID 12925687.{{cite journal}}: CS1 maint: PMC format (link)
  25. ^ Rapozzi, Valentina; Cogoi, Susanna; Spessotto, Paola; Risso, Angela; Bonora, Gian Maria; Quadrifoglio, Franco; Xodo, Luigi Emilio (2002-01). "Antigene Effect in K562 Cells of a PEG-Conjugated Triplex-Forming Oligonucleotide Targeted to thebcr/ablOncogene†". Biochemistry. 41 (2): 502–510. doi:10.1021/bi011314h. ISSN 0006-2960. {{cite journal}}: Check date values in: |date= (help)
  26. ^ a b c d Frank-Kamenetskii, Maxim D.; Mirkin, Sergei M. (1995). "Triplex DNA Structures" (PDF). Annu Rev Biochem. 64: 65–95. doi:10.1146/annurev.bi.64.070195.000433.
  27. ^ Bertucat, G.; Lavery, R.; Prévost, C. (1998-12). "A model for parallel triple helix formation by RecA: single-single association with a homologous duplex via the minor groove". Journal of Biomolecular Structure & Dynamics. 16 (3): 535–546. doi:10.1080/07391102.1998.10508268. ISSN 0739-1102. PMID 10052612. {{cite journal}}: Check date values in: |date= (help)
  28. ^ Chen, Jin; Tang, Qingnan; Guo, Shiwen; Lu, Chen; Le, Shimin; Yan, Jie (2017-09-29). "Parallel triplex structure formed between stretched single-stranded DNA and homologous duplex DNA". Nucleic Acids Research. 45 (17): 10032–10041. doi:10.1093/nar/gkx628. ISSN 0305-1048. PMC 5622322. PMID 28973442.{{cite journal}}: CS1 maint: PMC format (link)
  29. ^ Camerini-Otero, R.Daniel; Hsieh, Peggy (1993-04). "Parallel DNA triplexes, homologous recombination, and other homology-dependent DNA interactions". Cell. 73 (2): 217–223. doi:10.1016/0092-8674(93)90224-e. ISSN 0092-8674. {{cite journal}}: Check date values in: |date= (help)
  30. ^ "A Molecular Model for RecA-Promoted Strand Exchange via Parallel Triple-Stranded Helices". Biophysical Journal. 77 (3): 1562–1576. 1999-09-01. doi:10.1016/S0006-3495(99)77004-9. ISSN 0006-3495.
  31. ^ Yang, Haijuan; Zhou, Chun; Dhar, Ankita; Pavletich, Nikola P. (10 2020). "Mechanism of strand exchange from RecA-DNA synaptic and D-loop structures". Nature. 586 (7831): 801–806. doi:10.1038/s41586-020-2820-9. ISSN 1476-4687. PMID 33057191. {{cite journal}}: Check date values in: |date= (help)
  32. ^ a b c Felsenfeld, G.; Davies, David R.; Rich, Alexander (1957-04). "FORMATION OF A THREE-STRANDED POLYNUCLEOTIDE MOLECULE". Journal of the American Chemical Society. 79 (8): 2023–2024. doi:10.1021/ja01565a074. ISSN 0002-7863. {{cite journal}}: Check date values in: |date= (help)
  33. ^ Hanvey, J. C.; Shimizu, M.; Wells, R. D. (1988-09-01). "Intramolecular DNA triplexes in supercoiled plasmids". Proceedings of the National Academy of Sciences. 85 (17): 6292–6296. doi:10.1073/pnas.85.17.6292. ISSN 0027-8424. PMC 281955. PMID 3413097.{{cite journal}}: CS1 maint: PMC format (link)
  34. ^ Mirkin, S. M.; Lyamichev, V. I.; Drushlyak, K. N.; Dobrynin, V. N.; Filippov, S. A.; Frank-Kamenetskii, M. D. (1987-12). "DNA H form requires a homopurine–homopyrimidine mirror repeat". Nature. 330 (6147): 495–497. doi:10.1038/330495a0. ISSN 1476-4687. {{cite journal}}: Check date values in: |date= (help)
Retrieved from "https://en.wikipedia.org/w/index.php?title=User:Scalvert2000/H-DNA&oldid=994521581"