A structural study of M-DNA

In alkaline conditions, a complex called M-DNA is formed between a divalent metal ion, cobalt, nickel or zinc, and duplex DNA. The rate of formation and stability of M-DNA is dependent on many factors, including but not limited to temperature, pH, DNA sequence, and metal or DNA concentrations. It has been hypothesized that the divalent metal ions intercalate into the helix and replace the imino protons involved in the hydrogen bonding of both G-C and A-T base pairs. The complex is thought to have a double helical structure that is similar to B-DNA. The presence of the divalent metal ions and a more compact structure may contribute to M-DNA’s remarkable ability to behave as a molecular wire. Because M-DNA is so similar to B-DNA, it adheres to the same rules with regards to self-assembly. The ability of DNA to self-assemble and the electronic conduction of M-DNA are ideal properties for nanotechnology of the future. M-DNA may eventually be used to detect the presence of biologically important small molecules and DNA binding proteins that block the flow of electrons. However, before M-DNA will be widely accepted, it is necessary to obtain an accurate 3-dimensional structure by X-ray crystallography and modelling. In this work interactions between divalent cobalt, nickel or zinc with duplex DNA were studied using two different experimental methods; namely, X-ray crystallography and extended X-ray absorption fine structure spectroscopy. First, crystals of the sequence d[GA(5FU)(5FU)AA(5FU)C] and d[CG(5FU)G(5FU)GCACACG] complexed with divalent metals were grown in M-DNA favouring conditions. Both of the sequences gave crystals that provided diffraction data that were analyzed by molecular replacement using B-DNA models. Unfortunately, the quality of the diffraction was not high enough with either sequence to locate metal binding or to determine a model for M-DNA. Second, X-ray absorption spectroscopy data were analyzed for the Ni2+ K-edge of both Ni2+ M and B-DNA. Several differences between the M and the B-DNA data were noticed and some final bond distances were established.

Name thesis:degree_name

Master of Science (M.Sc.)

Level thesis:degree_level

Masters

Discipline thesis:degree_discipline

Biochemistry

Grantor

University of Saskatchewan

Year dc:date.issued

2006

Author dc:creator

• Hoffort, Angela

Advisors dc:contributor.advisor

• Lee, Jeremy S.
• Delbaere, Louis T. J.

• nucleic acid structure
• EXAFS
• DNA metal interactions
• crystallography
• M-DNA

Language dc:language.iso

en_US

Handle dc:identifier.uri

https://hdl.handle.net/10388/etd-07172006-181826

OAI identifier oai:identifier

oai:harvest.usask.ca:10388/etd-07172006-181826