Multistranded DNA structures

Gilbert, Dara E.; Feigon, Juli

doi:10.1016/s0959-440x(99)80041-4

Cited by 279 publications

(224 citation statements)

References 52 publications

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“…There are studies suggesting that certain mismatches are allowed or can be accommodated during triplex DNA formation. (36,53,54) However, such mismatches indeed make the task of proving the nature of the non-B structure difficult. Alternatively, this could be a site of rapid melting and reannealing (breathing), which may transiently adopt a non-B conformation.…”

Section: The Bcl-2 Mbr Forms a Non-b Dna Structurementioning

confidence: 99%

DNA structures at chromosomal translocation sites

Raghavan

Lieber

2006

BioEssays

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SummaryIt has been unclear why certain defined DNA regions are consistently sites of chromosomal translocations. Some of these are simply sequences of recognition by endogenous recombination enzymes, but most are not. Recent progress indicates that some of the most common fragile sites in human neoplasm assume non-B DNA structures, namely deviations from the Watson-Crick helix. Because of the single strandedness within these non-B structures, they are vulnerable to structure-specific nucleases. Here we summarize these findings and integrate them with other recent data for non-B structures at sites of consistent constitutional chromosomal translocations.

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Section: The Bcl-2 Mbr Forms a Non-b Dna Structurementioning

confidence: 99%

DNA structures at chromosomal translocation sites

Raghavan

Lieber

2006

BioEssays

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“…and function of DNA and RNA. Mono-and divalent cations are thought to induce bending in DNA duplexes [1,2], and are also known to stabilize triplex [3,4], and quadruplex [5,6] structures. Metal cations are also required for the proper folding and function of many forms of RNA, including most ribozymes [7,8].…”

mentioning

confidence: 99%

Charge state-dependent fragmentation of oligonucleotide/metal complexes

Keller

Brodbelt

2005

J. Am. Soc. Mass Spectrom.

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Collision-activated dissociation (CAD) has been employed to assess the gas-phase fragmentation behavior of a series of 1:1 oligodeoxynucleotide (ODN):metal complexes over a range of charge states, using several ten-residue ODNs and a wide array of alkali, alkaline earth, and transition metals. For parent species in low to intermediate charge states, complexation with Ca ϩ2 , Sr ϩ2 , or Ba ϩ2 altered the relative intensity of M-B species, promoting loss of cytosine over loss of guanine. The relative intensities of sequence ions were largely unaffected. This behavior was most prevalent for isomeric sequences with complementary residues at the 5=-and 3=-termini, suggesting that metal complexation may change the gas-phase conformation and/or conformational dynamics for some sequences. In higher charge states, some ODN/ Ba ϩ2 complexes produced abundant fragment ions corresponding to metallated a n Ϫm species, which are not commonly observed in CAD mass spectra for deprotonated ODNs. The formation of these ions was most favored for complexes between Ba ϩ2 and ODN sequences with a thymine residue at Position 6. Literature precedent exists for the formation of a n Ϫm ions from sequences in which covalent modification generates one or more neutral sites along the phosphate backbone. ODN/metal adducts in high charge states possess only a few acidic protons, and the juxtaposition of these neutral phosphate groups near thymine residues and the bound Ba ϩ2 ion may direct formation of the metallated a n Ϫm species. and function of DNA and RNA. Mono-and divalent cations are thought to induce bending in DNA duplexes [1,2], and are also known to stabilize triplex [3,4], and quadruplex [5,6] structures. Metal cations are also required for the proper folding and function of many forms of RNA, including most ribozymes [7,8]. The interactions of DNA with several natural products [9] and synthetic drugs and drug candidates [10,11] are known to be metal-mediated.Mass spectrometry (MS) is well-established as a useful tool for the structural characterization and sequencing of nucleic acids [12][13][14], and has also been employed to characterize a number of nucleic acid/metal ion interactions [15]. Several previous studies have focused on the interactions of the anticancer therapeutic cisplatin or its derivatives with DNA [16 -22]. Relatively few studies have addressed binary interactions of nucleic acids and metal cations [23][24][25][26][27]. Most of these studies have focused primarily on complexes with the smaller alkali and alkaline earth metals (e.g., Na ϩ , Mg ϩ2 ), although a few complexes with transition metals [25,26] or f-block elements [23,25] have also been investigated. The fragmentation behavior of these complexes has been characterized using parent species in relatively low charge states (often Ϫ2), but intermediate and high charge state precursors have not been studied. A more complete characterization of the entire charge state envelope produced by electrospray ionization would not only enhance our theoretical underst...

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“…In most cases, little direct information concerning the location of the stabilizing cation is available from such studies. One exception is the recent report identifying the location of bound NH 4 + cations between adjacent quartets in the [d(G 4 T 4 G 4 )] 2 quadruplex, via cation-DNA 1 H-1 H NOE's (7). This approach, however, is not readily extended to metal ions.…”

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confidence: 99%

“…This approach, however, is not readily extended to metal ions. More recently, solidstate 23 Na NMR techniques have been exploited to characterize the number and type of bound metal ions in the [d(TG 4 T)] 4 quadruplex (8), although quantitative distance information was not available.…”

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confidence: 99%

Pb EXAFS Studies on DNA Quadruplexes: Identification of Metal Ion Binding Site

et al. 2002

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Nucleic acid quadruplexes are composed of guanine quartets stabilized by specific metal ions. X-ray diffraction can provide high-resolution information on the structure and metal binding properties of quadruplexes, but only if they can be crystallized. NMR can provide detailed information on the solution structure of such quadruplexes but little quantitative data concerning the metal binding site. Here we apply extended X-ray absorption fine structure (EXAFS) measurements to characterize the metal ion binding site, in frozen solution, of the unimolecular quadruplex formed by the thrombin binding aptamer, d(G 2 T 2 G 2 TGTG 2 T 2 G 2 ) (TBA), in the presence of Pb 2+ ions. The Pb L III -edge X-ray absorption spectrum of this metal-DNA complex is very similar to that we obtain for a Pb 2+ -stabilized quartet system of known structure constructed from a modified guanine nucleoside (G1). The Fourier transforms of the Pb 2+ complexes with both TBA and G1 show a first-shell interaction at about 2.6 Å, and a weaker, broader shell at 3.5-4.0 Å. Quantitative analysis of the EXAFS data reveals the following: (i) very close agreement between interatomic distances at the metal coordination site for the Pb 2+ -G1 complex determined by EXAFS and by X-ray crystallography; (ii) similarly close agreement between interatomic distances measured by EXAFS for the Pb 2+ -G1 and Pb 2+ -TBA complexes. These results provide strong evidence for binding of the Pb 2+ ion in the region between the two quartets in the Pb 2+ -TBA complex, coordinated to the eight surrounding guanine O6 atoms. The specific binding of Pb 2+ to DNA examined here may be relevant to the genotoxic effects of this environmentally important heavy metal. Furthermore, these results demonstrate the utility of EXAFS as a method for quantitative characterization of specific metal binding sites in nucleic acids in solution.Metal ion-DNA interactions are important in nature, often impacting the genetic material's structure and function. To better understand the molecular details of these interactions, it is essential that we have a reliable picture of the metal ion coordination site. This is not always so straightforward. Thus, X-ray diffraction can provide high-resolution information on the structure and metal binding properties of nucleic acids, but only if diffraction-quality crystals can be obtained. NMR can provide detailed information on solution structure, but usually little quantitative data concerning the metal binding site. This paper describes how extended X-ray absorption fine structure (EXAFS) 1 measurements can be used to gain detailed information about a Pb 2+ binding site within a folded DNA oligonucleotide.DNA and RNA can form quadruplex structures in the presence of certain metal ions, based on the guanine quartet, which is shown in Figure 1A. Only a small number of X-ray crystal structure determinations on quadruplexes have been reported, and these have located the metal binding site in the region between two quartet stacks, or coplanar with one...

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Multistranded DNA structures

Cited by 279 publications

References 52 publications

DNA structures at chromosomal translocation sites

DNA structures at chromosomal translocation sites

Charge state-dependent fragmentation of oligonucleotide/metal complexes

Pb EXAFS Studies on DNA Quadruplexes: Identification of Metal Ion Binding Site

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