ja305384c_si_001.pdf (175.79 kB)
Beads-on-a-String Structure of Long Telomeric DNAs under Molecular Crowding Conditions
journal contribution
posted on 2012-12-12, 00:00 authored by Haiqing Yu, Xiaobo Gu, Shu-ichi Nakano, Daisuke Miyoshi, Naoki SugimotoThe structure and stability of long telomeric DNAs, (T2AG3)n (n =
4–20), were studied under dilute and molecular crowding conditions
in the presence of Na+ and K+. Structural analysis
showed that the long telomeric DNAs formed intramolecular G-quadruplexes
under all conditions. In the presence of Na+, the telomeric
DNAs formed an antiparallel G-quadruplex under both dilute and molecular
crowding conditions. However, in the presence of K+, molecular
crowding induced a conformational change from mixed to parallel. These
results are consistent with numerous structural studies for G-quadruplex
units under molecular crowding conditions. Thermodynamic analysis
showed that G-quadruplexes under the molecular crowding conditions
were obviously more stable than under dilute condition. Interestingly,
this stabilization effect of molecular crowding was reduced for the
longer telomeric DNAs, indicating that the G-quadruplex structure
of long telomeric DNAs is not as stable under molecular crowding conditions,
as implied from the large stabilization of isolated G-quadruplex units
as previously reported. Moreover, a hydration study revealed that
upon structure folding, the interior of a G-quadruplex unit was dehydrated,
whereas the linker between two units was more hydrated. It is thus
possible to propose that the linkers between G-quadruplex units are
ordered structures but not random coils, which could have an important
influence on the stability of the entire structure of long telomeric
DNAs. These results are significant to elucidate the biological characteristics
of telomeres, and can aid in the rational design of ligands and drugs
targeting the telomere and related proteins.