Campus Only Senior Thesis
W.M. Keck Science Department
© 2014 Georgia A. Macy
Methylation is involved in the regulation of varied biological processes, from cancer to embryonic development. In B-DNA, methylation can alter the frequency with which a dinucleotide step samples one of two substates: BI and BII. Changing the BI-BII equilibrium can in turn affect the ability of proteins to bind to DNA, which may ultimately alter the transcription of genes. Using MD simulations, we evaluate the effects of cytosine methylation on the BI-BII equilibrium and the RMS atomic fluctuations of the backbone of two sequences: (GC)5 and the Dickerson dodecamer (DD). Methylation in (GC)5 stabilizes the BII state in CpG steps and stabilizes the BI state in GpC steps, but the BII state is always less favored than the BI state. The activation energy between the BI/BII states in (GC)5 increases in GpC steps and decreases in CpG steps upon methylation, indicating that backbone dynamics are affected by methylation in a step-dependent manner. The DD simulations suggest that methylation stabilizes the BII state in both CpG and GpC steps, although more sampling is needed to determine the significance of these results. Methylation has little effect on the atomic fluctuations of the backbone in (GC)5 or DD simulations. Thus, in these sequences, methylation does not uniformly stabilize one state, nor does methylation stabilize the state that is favored in the native sequence.
Macy, Georgia A., "The Effects of CpG Methylation on BI-BII Equilibrium in DNA" (2014). Scripps Senior Theses. 378.
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