Molecular structure of a left-handed double helical DNA fragment at atomic resolution

Wang, A H; Quigley, Gary J.; Kolpak, Francis J.; Crawford, James L.; Boom, Jacques H. van; Marel, Gijs van der; Rich, Alexander

doi:10.1038/282680a0

Cited by 2,035 publications

(1,155 citation statements)

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“…Netropsin increases cross-linking of angelicin (Lown & Sim, 1978), perhaps by helping stabilize the unusual conformation. (d) Finally, the discovery that d(C-G)yd(C-G), can form the novel "Z" structure (Wang et al, 1979) raises the possibility that, without gross perturbation from bound molecules, DNA itself can form stable alternative structures dependent on base sequence. Because all these experiments were done on T4 DNA, we have not excluded the possibility that one of the two putative types of cross-linking sites is characterized by the presence of glucosylated hydroxymethylcytosine near the site or by the type of glucosylation.…”

Section: Discussionmentioning

confidence: 99%

Low-level psoralen-deoxyribonucleic acid crosslinks induced by single laser pulses

Johnston¹,

Hearst²

1981

Biochemistry

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While many intercalated psoralens require a 1.3-ps relaxation time between absorption of the first and second photons for cross-link formation to occur, some psoralens can form cross-links within the lifetime of a 10-ns laser pulse. This effect is largely or completely oxygen independent. Structural, kinetic, and energetic considerations suggest that the 1.3-ps delay may be due to a conformational change in the deoxyribonucleic acid (DNA) at the intercalation site which could be required for proper alignment of the double bonds which react in the second photoreaction. The cross-links which can form with single pulses of light may result from intercalation complexes which are already in a conformation such that, E o r a l e n s are skin-photosensitizing compounds (furocoumarins), which intercalate between the base pairs of double-helical nucleic acids and, upon absorption of long-wave UV light, can form cyclobutane adducts to adjacent pyrimidines. Capable of photoreacting at both ends of the molecule, a favorably positioned psoralen can cross-link the double helix by reacting with pyrimidines on opposite strands lying above and below the intercalation site.In earlier work (Johnston et al., 1977), we utilized single pulses from a ruby laser (A = 347 nm) to produce monoadducts between 4'-(aminomethyl)-4,5',8-trimethylpsoralen (AMT)' and bacteriophage T4 DNA, with no cross-links detectable.Our interpretation of this result postulated the existence of an intermediate excited state which "decays" into a monoadduct capable of further photoreaction @e., forming a cross-link) only after a time interval long compared to the 15-1s duration of the laser pulse. We have measured the l / e time required for formation of a "cross-linkable" monoadduct to be 1.3 hs (Johnston et al., 1980) and suggested that a conformational change is required after formation of a monoadduct before it is capable of forming a cross-link. In the course of this measurement, which required the use of different laser sources, higher pulse energy, and an increased accuracy in cross-link detection over the original work, it was found that some cross-links are formed by two pulses of light spaced closer than 100 ns and indeed by single 15-11s pulses. Spacing two pulses farther apart than 1 ps simply increases the yield of cross-links, dramatically at the ruby wavelength and less dramatically at the wavelength of the Nd-YAG laser (355 nm) used in the two-pulse experiments. In the present work we have analyzed this effect and suggest that a certain subpopulation of intercalated psoralens is capable of forming a within 20 ns after absorption of an initial photon, a monoadduct is formed which can absorb a second photon and thence result in a cross-link. These intercalation sites may be distinguished by the type and sequence of base pairs at the site or, alternatively, at the moment of the pulse, random motions of the DNA may have brought those sites into a conformation which allows cross-linking without the 1.3-ps delay. Unlike "ordinary" cross-link...

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Section: Discussionmentioning

confidence: 99%

Low-level psoralen-deoxyribonucleic acid crosslinks induced by single laser pulses

Johnston¹,

Hearst²

1981

Biochemistry

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“…As already reported in the introduction to this paper, the analysis of the crystallographic data and the construction of the corresponding models ha\ e suggested to their authors [1,2] that a number of reactive sites on the bases should be more accessible in Z DNA than in its B DNA counterpart. The observation concern\ in particular atoms such as N7(G), O6(G) and CX(G) known to be the receptor sites for covalent bond formation with ;I scries of carcinogenic compounds (see e.g.…”

Section: Sitr Potrn Finand Urid a Ccessih Ili F Iesmentioning

confidence: 78%

“…structure of Z D N A indicated that certain of its base-pair atoms on its convex face are unusually exposed, the hypothesis was put forward [1,2] that if Z-DNA segments were interspersed within a B-DNA chain, these atoms could represent privileged targets for appropriate attacking species, e.g. C-8 of guanine, C8(G), could be wch a target for the carcinogen N-2-acetylaminofluorene which preferentially attacks this site.…”

Section: Camer D(c-g-c-g-a-a-t-t-c-g-c-g) Which Although Cor-mentioning

confidence: 99%

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Two Aspects of DNA Polymorphism and Microheterogeneity:

Pullman

Lavery

Pullman

1982

European Journal of Biochemistry

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Polymorphism and microheterogeneity of DNA appear today as being capable of having important biological consequences. This paper presents a synthetic view of two major properties of the main known forms of DNA (A, B, alternating B, C, D and Z), namely their molecular electrostatic potentials and stcric accessibilities.Variations in these properties are explained in terms of the conformational changes involved and deductions are drawn concerning their influence on the interactive properties of DNA with external agents.Since the early studies of D N A structure it has been recognized that this biopolymer may exist in different conformational forms, dependent on the external conditions to which it is exposed (humidity, salt concentration, etc.). These allomorphic forms are designated by the letters, A, B, C etc., the B form being currently considered as biologically the most significant.More recently it has become evident that conformational changes may also be induced by varying the sequence of the base pairs, a situation which necessarily leads to the consideration of a possible microheterogeneity of native DNA as a function of the order of the base pairs along its axis. Two recent works seem to have had a particularly strong influence in bringing this situation to light. One is the discovery of a family of left-handed DNA double helices, termed Z DNAs, found in the crystal of the self-complementary hexamer d(C-G-C-G-C-G) [1,2] and in the high salt solution of poly(dG-dC) . poly(dG-dC) [3]. The left-handedness, apparently characteristic of this sequence, as opposed to the usual right-handedness of DNAs, is a particularly impressive example of a sequence-dependent conformational change. The second discovery concerns the determination of the X-ray structure of the single crystal of the self-complementary dode- (C-G-C-G-A-A-T-T-C-G-C-G) which, although cor-responding to an overall B-DNA structure, exhibits many local deviations from it [4,5]. Further, more direct evidence of a non-uniform backbone conformation of DNA has been obtained by 31P NMR spectroscopy [6] and there is also evidence for the possible coexistence of the A and B conformations along a synthetic nucleic acid duplex [7,8].Such a heterogeneity of DNA is bound to have an important influence on its biochemical and, consequently, its biological behavior and, particularly, on the specificity of its interaction or association with external agents. In fact, it is known that, for example, the oligopeptide antibiotics netropsin and distamycin A have very different affinities for differently sequenced DNAs or for the different DNA conformers, A and B [9-111. Similarly, when the establishment of the Ahbreviutions. C8(G), C-8 of guanine, and similarly for the otherreactive atoms of the purines and pyrimidines. structure of Z D N A indicated that certain of its base-pair atoms on its convex face are unusually exposed, the hypothesis was put forward [1,2] that if Z-DNA segments were interspersed within a B-DNA chain, these atoms could represent privileged targets...

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“…However, X-rays studies on crystals of alternating d(CpG)-DNA fragments and on fibers of poly(dG-dC) • poly(dG-dC) have demonstrated a left-handed double helix termed Z-DNA [1][2][3][4]. In solution, poly-(dG-dC) • poly(dG-dC) can adopt the B-or Z-form depending upon the ionic strength of the medium [5][6][7][8][9].…”

Section: Introductionmentioning

confidence: 99%