Nucleic Acids Research Advance Access originally published online on April 9, 2009
Nucleic Acids Research 2009 37(11):3625-3634; doi:10.1093/nar/gkp216
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Nucleic Acids Research, 2009, Vol. 37, No. 11 3625-3634
© 2009 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Structural Biology |
Dramatic effect of single-base mutation on the conformational dynamics of human telomeric G-quadruplex
1Department of Physics and Astronomy and 2Centre for Subwavelength Optics, Seoul National University, San 56-1, Shillim-dong, Kwanak-gu, Seoul, 151-742, South Korea
*To whom correspondence should be addressed. Tel: +82 2 889 1295; Fax: +82 2 884 3002; Email: jayil{at}phya.snu.ac.kr
Received December 12, 2008. Revised February 23, 2009. Accepted March 17, 2009.
Guanine-rich DNA sequences can form G-quadruplexes. These four-stranded structures are known to form in several genomic regions and to influence certain biological activities. Sometimes, the instability of G-quadruplexes causes the abnormal biological processes. Mutation is a culprit for the destabilization of G-quadruplexes, but the details of mutated G-quadruplexes are poorly understood. In this article, we investigated the conformational dynamics of single-base mutated human telomeric G-quadruplexes in the presence of K+ with single-molecule FRET spectroscopy. We observed that the replacement of single guanine by thymine in a G-track induces various folded structures, i.e. structural polymorphism. Moreover, direct observation of their dynamics revealed that a single-base mutation causes fast unfolding of folded states under physiological conditions. Furthermore, we found that the degree of destabilization varies according to mutation positions. When the central guanine of a G-track is replaced, the G-quadruplexes unfold quickly at any K+ concentrations and temperature. Meanwhile, outer-quartet mutated G-quadruplexes have heterogeneous dynamics at intermediate K+ concentrations and longstanding folded states at high K+ concentrations. Several factors such as base-stacking interaction and K+ coordination are responsible for the different dynamics according to the mutation position.
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