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Title: X-ray crystallographic studies of DNA structures : conformational changes induced by metal cations, organic ligands and sequence variation
Author: Gan, Yu
ISNI:       0000 0001 3487 5241
Awarding Body: University of Reading
Current Institution: University of Reading
Date of Award: 2007
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This thesis concentrates on the study of DNA structures by X-ray crystallography. The first chapter introduces the molecules under study; whilst chapter two describes the theories and methodologies that are closely involved. The following three chapters contain the main results and describe eight refined structures. Chapter three examines ion influences upon an unusual non-planar G/C quadruplex formed by the heptamer nucleotide d(GCATGCT), in which the highly carcinogenic element nickel has be.en found to cause dramatic distortions in this otherwise very stable DNA structure: Chapter four is focused on the DNA-intercalator complexes formed between the hexamer nucleotide d(CGTACG) and two bis-acridine derivatives that differ at their linkers in terms of length and charge. It was found that the bis-acridine compound with a linker consisting of a nitrogen plus six carbon atoms was able to crosslink the DNA m~lecules in a novel wa.y, in which the acridine chromophore is rotated around its plane normal by 1800 away from the conformation found previously in the monomers and one side-chain attached bis-acridine derivatives. In the complex of the same oligonucleotide and another bis-acridine' derivative with a longer linker in the presence of C02 +, the best electron density around the ligand, compared with all the other reported analogues, was obtained from the in-house diffractometer. Chapter five describes two A-DNA structures formed by the same sequences that are crystallised in different spacegroups. The novel choice of the sequences was inspired by a recent publication reporting a statistical analysis of recombination sequences in the human genome. The chosen decamer nucleotide contains the recombination hotspot heptamer CCTCCCT. ., Chapter six presents the results of G-quadruplex crystallisation studies, and some preliminary X-ray diffraction data. Chapter seven, as the last chapter of the thesis, , lists the ongoing projects and describes future work.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available