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Lee, Ja Yil
School of Life Sciences
Research Interests
  • Investigated eukaryotic homologous recombination.

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Dramatic effect of single-base mutation on the conformational dynamics of human telomeric G-quadruplex

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Title
Dramatic effect of single-base mutation on the conformational dynamics of human telomeric G-quadruplex
Author
Lee, Ja YilKim, D. S.
Issue Date
2009-06
Publisher
OXFORD UNIV PRESS
Citation
NUCLEIC ACIDS RESEARCH, v.37, no.11, pp.3625 - 3634
Abstract
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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DOI
10.1093/nar/gkp216
ISSN
0305-1048
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