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Cobalt, nickel and zinc-DNA interactions : a structural study

dc.contributor.advisorDelbaere, Louis T. J.en_US
dc.contributor.advisorLee, Jeremy S.en_US
dc.creatorLabiuk, Shaunivan Leeen_US
dc.date.accessioned2008-10-14T09:18:35Zen_US
dc.date.accessioned2013-01-04T05:01:16Z
dc.date.available2009-11-24T08:00:00Zen_US
dc.date.available2013-01-04T05:01:16Z
dc.date.created2003-08en_US
dc.date.issued2003-08en_US
dc.date.submittedAugust 2003en_US
dc.description.abstractM-DNA is a complex between DNA and cobalt(II), nickel(II) or zinc(II) that forms under alkaline conditions. It has been postulated that the imino proton of guanine or thymine is replaced by the metal cation in each base-pair. The complex is thought to maintain a double-helical structure similar to B-DNA but has unusual properties. M-DNA acts as an electron conductor making it a potential candidate for future nanotechnology applications. In this work the interactions of cobalt(II), nickel(II) and zinc(II) with DNA were studied. This was done in order to gain knowledge concerning the interactions of these metal cations with B-DNA and to assess aspects of the proposed M-DNA structural model. Firstly, experiments that demonstrated ionizing or ultraviolet radiation induced interstrand crosslinking in M-DNA are consistent with the hypothesis that M-DNA maintains a double-helical structure in which guanine binds with cytosine and adenine with thymine. These experiments also provide new insights into the effects of radiation on DNA in the presence of various metal ions at physiological and alkaline pHs. Secondly, a titration experiment was performed in which it was shown that for each metal cation that binds to M-DNA, approximately one proton is released. This result is consistent with the hypothesis that imino protons are released during M-DNA formation. Thirdly, crystals of the sequence d(GGCGCC) complexed with cobalt, nickel and zinc were grown. They did not grow in conditions above pH 8.1 and thus do not provide a solid state structural model for M-DNA. Interestingly, x-ray diffraction experiments revealed metal binding only to terminal N(7) positions of guanine residues with coordinated water molecules interacting with neighboring guanine residues affecting the propeller twist. Though the crystals had a high solvent content, it is interesting that the few interactions involving the metal cations were sufficient to stabilize the crystal lattice. Finally, conditions for growing crystals with DNA containing 5-fluorouracil at alkaline pH in the presence of cobalt were also discovered. This is a critical step because the presence of 5-fluorouracil allows DNA sequences to more readily form M-DNA at lower pH.en_US
dc.identifier.urihttp://hdl.handle.net/10388/etd-10142008-091835en_US
dc.language.isoen_USen_US
dc.titleCobalt, nickel and zinc-DNA interactions : a structural studyen_US
dc.type.genreThesisen_US
dc.type.materialtexten_US
thesis.degree.departmentBiochemistryen_US
thesis.degree.disciplineBiochemistryen_US
thesis.degree.grantorUniversity of Saskatchewanen_US
thesis.degree.levelDoctoralen_US
thesis.degree.nameDoctor of Philosophy (Ph.D.)en_US

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