Differential Effects of Cyclopolyamines on the Stability and Conformation of Triplex DNA

Antony, Thomas; Musso, Marco; Hosseini, Mir Wais; Brand, Guy; Greenfield, Norma J.; Thomas, Thresia; Dyke, Michael W. Van; Thomas, T.

doi:10.1089/oli.1.1999.9.13

Cited by 4 publications

(4 citation statements)

References 53 publications

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“…The elasticity of the DNA was correlated to both its interaction with polyamines [43] and temperature. Melting experiments demonstrated that polyamines stabilize the DNA structure with an ability that is a function of the polyamine chain length [24–26]. Moreover, the melting entropy of DNA was determined by measuring the overstretching force of single molecules of DNA [22,23].…”

Section: Resultsmentioning

confidence: 99%

“…Temperature is an additional factor capable of affecting DNA conformation. It has been reported that (a) an increase of a few°C is associated with a reduction in the overstretching forces of the DNA strands [22,23], (b) that the DNA melting temperature is directly correlated with the chain length of interacting polyamines [24][25][26][27] and (c) that a transition of the DNA chain from a dispersed coil state to a condensed-collapsed state parallels an increase in temperature [28]. These findings draw attention to the relationship existing between temperature and stabilization, aggregation, elasticity and conformational transition of the DNA, all phenomena closely linked to DNA protection and influenced by polyamines.…”

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Nuclear aggregates of polyamines are supramolecular structures that play a crucial role in genomic DNA protection and conformation

D’Agostino¹,

Pietro²,

Luccia

2005

The FEBS Journal

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Polyamines interact with DNA phosphate groups by means of nonspecific electrostatic bonds [1]. This interaction has been shown to result in the protection of small DNA molecules from common damaging agents, such as ionizing radiation and reactive oxygen species [2,3]. Polyamines in solution with polynucleotides have also been shown to inhibit the activity of endonucleases, including DNase I [4][5][6][7]. The protective ability of polyamines is attributable not only to the formation of a steric barrier against DNA-damaging agents, but also to their property to condense the DNA. In fact, polyamines, like other cations, induce DNA condensation as a consequence of the inhibition of > 90% of DNA negative charges [8]. Analogous in vivo experiments have demonstrated that spermine and, to a lesser extent, spermidine, prevent DNA fragmentation and the onset of apoptosis. Protection from enzymatic cleavage appears to be the result of a modified chromatin arrangement, rather than inhibition of the endonuclease activity [9].Condensation of DNA in the presence of polyamines has also been proposed to be instrumental in genome packaging [10]. This should be regarded of crucial importance if we consider that the total length of cellular DNA is 1 m, whereas the size of the nucleus is in the range of several micrometers [11]. However, condensation should not be considered as a static state, as the elasticity is a mechanical property of the DNA, indispensable to cellular processes such as replication and transcription [12,13]. For these reasons the DNA strands in vivo, at the same time, must be packaged and protected, but not restrained.The structural impact of polyamines on DNA is also supported by the evidence that these compounds induce, on polynucleotides, a transition from the rightoriented B-form to the left-handed Z-form [14,15]. Such an effect might be important for DNA physiology, as a tight connection occurs between transcriptional activity on DNA and the acquisition of a Z-form [16]. In a previous study we showed that natural polyamines interact in the nuclear environment with phosphate groups to form molecular aggregates [nuclear aggregates of polyamines (NAPs)] with estimated molecular mass values of 8000, 4800 and 1000 Da. NAPs were found to interact with genomic DNA, influence its conformation and interfere with the action of nucleases. In the present work, we demonstrated that NAPs protect naked genomic DNA from DNase I, whereas natural polyamines (spermine, spermidine and putrescine) fail to do so. In the context of DNA protection, NAPs induced noticeable changes in DNA conformation, which were revealed by temperature-dependent modifications of DNA electrophoretic properties. In addition, we presented, for NAPs, a structural model of polyamine aggregation into macropolycyclic compounds. We believe that NAPs are the sole biological forms by which polyamines efficiently protect genomic DNA against DNase I, while maintaining its dynamic structure.Abbreviation NAP, nuclear aggregate of polyamines.

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Section: Resultsmentioning

confidence: 99%

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Nuclear aggregates of polyamines are supramolecular structures that play a crucial role in genomic DNA protection and conformation

D’Agostino¹,

Pietro²,

Luccia

2005

The FEBS Journal

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“…These include the covalent attachment of the duplex intercalator, pyrene, to the end of the oligonucleotide (along with sugar modification at the 2Ј position) or the incorporation of a phosphoramidate backbone consisting of substitution of a nitrogen for the 3Ј-bridging oxygen (31,45). Another approach to stabilize triplexes (and to aid entry into cells) is the use of polyamines either covalently attached to the TFOs or used in conjunction with the oligonucleotides during transfection (46,47).…”

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confidence: 99%

Chromosome Targeting at Short Polypurine Sites by Cationic Triplex-forming Oligonucleotides

Vásquez¹,

Dagle²,

Weeks³

et al. 2001

Journal of Biological Chemistry

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“…Furthermore, spermine induces the formation of triplex structures under conditions in which triplexes cannot be formed naturally. Various analogues of spermine have been synthesised and studied and some of them, such as cyclopolyamines, have been found to be more efficient . In light of those studies, the formation of DNA triplexes is affected by their length, the type of triplet, and the presence of cations or cationic compounds.…”

Section: Dna Triplexmentioning

confidence: 99%

Targeting Non-B-Form DNA in Living Cells

Zhou

2013

The Chemical Record

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Under certain conditions, repetitive DNA motifs have the potential to adopt non-B-form DNA structures, such as hairpins, triplexes, Z-DNA, quadruplexes, and i-motifs. Some non-B-form DNAs have been proposed to cause mutations and, consequently, participate in several biologically important processes, including regulation, evolution, and human disease. Advancement in the knowledge of specific interactions between molecules and non-B-form DNAs at the molecular level in living cells is important for understanding their biological functions. In this review, we describe the latest studies on molecules that target non-B-form DNAs in vivo, with a focus on Z-DNA, G-quadruplexes, triplexes, i-motifs, and hairpins.

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Differential Effects of Cyclopolyamines on the Stability and Conformation of Triplex DNA

Cited by 4 publications

References 53 publications

Nuclear aggregates of polyamines are supramolecular structures that play a crucial role in genomic DNA protection and conformation

Nuclear aggregates of polyamines are supramolecular structures that play a crucial role in genomic DNA protection and conformation

Chromosome Targeting at Short Polypurine Sites by Cationic Triplex-forming Oligonucleotides

Targeting Non-B-Form DNA in Living Cells

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