Properties of long human telomeric DNAs under cell-mimicking conditions.
We investigated the stability and structure of long telomeric DNAs derived from human, (TTAGGG)(n) (n=4-12) in the presence of 100 mM K(+) at 0 wt% or 20 wt% poly(ethylene glycol) 200 (PEG200) utilizing circular dichroism and UV melting analysis. The results showed that the values of enthalpy and entropy changes for the G-quadruplex formation of the telomeric DNAs whose repeat number was multiple of four, such as n=4, n=8, and n=12, increased gradually under the dilute condition (100 mM K(+)), demonstrating no interaction existed between the individual G-quadruplex units composing of four repeats. Therefore, the reasonable arrangement of the intramolecular G-quadruplexes formed by long telomeric DNAs (n> or =8) was proposed to be a bead-string structure in which the G-quadruplex units were connected each other by one TTA linker. Furthermore, the results of melting experiments demonstrated that thermodynamic stabilities of G-quadruplex structures of the long telomeric DNAs (n=5-12) are mostly independent of sequence length, although telomeric DNA including four repeats (n=4) is more stable than the longer ones. Moreover, the melting temperatures of the G-quadruplexes under the crowding condition (100 mM K(+) and 20 wt% PEG200) are higher than those under the dilute condition, indicating the crowding condition can increase the stability of G-quadruplex. These information are useful for researches of the telomere biology and a better development of therapeutic agents targeting telomeric DNAs.
Yu
Hai-Qing
HQ
Frontier Institute for Biomolecular Engineering Research, Konan University, 8-9-1 Okamoto, Higashinada-ku, Kobe 658-8501, Japan.
Miyoshi
Daisuke
D
Sugimoto
Naoki
N
D004247:DNA / Q000737:chemistry*; D054856:G-Quadruplexes; D006801:Humans; D011092:Polyethylene Glycols / Q000737:chemistry; D016615:Telomere / Q000737:chemistry*; D013816:Thermodynamics
D011092:Polyethylene Glycols; D004247:DNA