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Effects of Adenine Methylation on the Structure and Thermodynamic Stability of a DNA Minidumbbell
Authors:Liqi Wan  Sik Lok Lam  Hung Kay Lee  Pei Guo
Affiliation:1.MOE International Joint Research Laboratory on Synthetic Biology and Medicines, School of Biology and Biological Engineering, South China University of Technology, Guangzhou 510006, China;2.Department of Chemistry, The Chinese University of Hong Kong, Hong Kong SAR 999077, China;
Abstract:DNA methylation is a prevalent regulatory modification in prokaryotes and eukaryotes. N1-methyladenine (m1A) and N6-methyladenine (m6A) have been found to be capable of altering DNA structures via disturbing Watson–Crick base pairing. However, little has been known about their influences on non-B DNA structures, which are associated with genetic instabilities. In this work, we investigated the effects of m1A and m6A on both the structure and thermodynamic stability of a newly reported DNA minidumbbell formed by two TTTA tetranucleotide repeats. As revealed by the results of nuclear magnetic resonance spectroscopic studies, both m1A and m6A favored the formation of a T·m1A and T·m6A Hoogsteen base pair, respectively. More intriguingly, the m1A and m6A modifications brought about stabilization and destabilization effects on the DNA minidumbbell, respectively. This work provides new biophysical insights into the effects of adenine methylation on the structure and thermodynamic stability of DNA.
Keywords:DNA minidumbbell  DNA methylation  N1-methyladenine  N6-methyladenine  nuclear magnetic resonance spectroscopy
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