DNA stores the genetic information of almost all organisms and its integrity and stability are essential to life. Unfortunately, mutations can occur within the genome and causes genomic instability. Such mutations include but not limited to single nucleotide variation and large number nucleotides expansion. In this study, we used kinetic and calorimetric techniques to study the mechanisms underlying the two above mentioned mutations. We first investigated by kinetic technique that whether the hyperoxidized nucleotide dSpTP diastereomers, from the oxidation of the canonical dGTP in nucleotide pool, may contribute to the DNA mutation. We then used differential scanning calorimetry (DSC) to describe the thermodynamic parameters (ΔH, TΔS, and ΔG) of the non-canonical stem-loop hairpins formed by the trinucleotide repeat (TNR) sequences (CAG)n and (CTG)n, and also the canonical (CAG)n/(CTG)n duplexes, which are involved in the TNR expansion of several neurological disorders. The thermodynamic and kinetic parameters of hairpin to duplex conversion are also discussed. Finally, using DSC we characterized the thermal denaturation properties of nucleosome, the fundamental repeating unit of chromatin, with a special focus on the consequence of the expansion of CAG repeats.
Huang, Ji,
"From Nucleotide to Nucleosome: A Kinetic and Calorimetric Study of DNA"
(2016).
Chemistry Theses and Dissertations.
Brown Digital Repository. Brown University Library.
https://doi.org/10.7301/Z0QN655Q
