5-Methylcytosine Substantially Enhances the Thermal Stability of DNA Minidumbbells |
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| Authors: | Liqi Wan Jie Yi Prof. Dr. Sik Lok Lam Prof. Dr. Hung Kay Lee Prof. Dr. Pei Guo |
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| Affiliation: | 1. Department of Chemistry, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China;2. School of Biology and Biological Engineering, South China University of Technology, Guangzhou, Guangdong, 510006 China |
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| Abstract: | Minidumbbell (MDB) is a recently identified non-B DNA structure that has been proposed to associate with genetic instabilities. It also serves as a functional structural motif in DNA nanotechnology. DNA molecular switches constructed using MDBs show instant and complete structural conversions with easy manipulations. The availability of stable MDBs can broaden their applications. In this work, we found that substitutions of cytosine with 5-methylcytosine could lead to a significant enhancement in the thermal stabilities of MDBs. Consecutive methylations of cytosine in MDBs brought about cumulative stabilization with a drastic increase in the melting temperature by 23 °C. NMR solution structures of two MDBs containing 5-methylcytosine residues have been successfully determined and revealed that the enhanced stabilities resulted primarily from favorable hydrophobic contacts, more stable base pairs and enhanced base-base stackings involving the methyl group of 5-methylcytosine. |
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| Keywords: | DNA methylation DNA structures nanostructures NMR spectroscopy thermodynamics |
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