Fujimoto Takeshi, Nakano Shu-Ichi, Miyoshi Daisuke, Sugimoto Naoki
Faculty of Frontiers of Innovative Research in Science and Technology (FIRST), Konan University, 7-1-20 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan.
J Nucleic Acids. 2011;2011:857149. doi: 10.4061/2011/857149. Epub 2011 Sep 21.
Both cellular environmental factors and chemical modifications critically affect the properties of nucleic acids. However, the structure and stability of DNA containing abasic sites under cell-mimicking molecular crowding conditions remain unclear. Here, we investigated the molecular crowding effects on the structure and stability of the G-quadruplexes including a single abasic site. Structural analysis by circular dichroism showed that molecular crowding by PEG200 did not affect the topology of the G-quadruplex structure with or without an abasic site. Thermodynamic analysis further demonstrated that the degree of stabilization of the G-quadruplex by molecular crowding decreased with substitution of an abasic site for a single guanine. Notably, we found that the molecular crowding effects on the enthalpy change for G-quadruplex formation had a linear relationship with the abasic site effects depending on its position. These results are useful for predicting the structure and stability of G-quadruplexes with abasic sites in the cell-mimicking conditions.
细胞环境因素和化学修饰都会对核酸的性质产生关键影响。然而,在模拟细胞的分子拥挤条件下,含有无碱基位点的DNA的结构和稳定性仍不清楚。在此,我们研究了分子拥挤对包含单个无碱基位点的G-四链体结构和稳定性的影响。圆二色性结构分析表明,PEG200引起的分子拥挤不会影响有无无碱基位点的G-四链体结构的拓扑结构。热力学分析进一步表明,随着单个鸟嘌呤被无碱基位点取代,分子拥挤对G-四链体的稳定程度降低。值得注意的是,我们发现分子拥挤对G-四链体形成的焓变的影响与无碱基位点的影响(取决于其位置)呈线性关系。这些结果有助于预测在模拟细胞条件下含有无碱基位点的G-四链体的结构和稳定性。