ALTERATION OF RELATIVE STABILITY OF DA-DT AND DG-DC BASE PAIRS IN DNA
ALTERATION OF RELATIVE STABILITY OF DA-DT AND DG-DC BASE PAIRS IN DNA
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DOI：
10.1073/pnas.70.2.298
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发表时间：
1973-01-01
影响因子：
11.1
通讯作者：
VONHIPPE.PH
中科院分区：
文献类型：
--
作者：
MELCHIOR, WB;VONHIPPE.PH
几个小的烷基铵离子可以消除，甚至逆转 DNA 转变温度通常对碱基组成的依赖性。例如，在 3 M 四甲基氯化铵或 2.4 M 四乙基氯化铵中，不同碱基组成的 DNA 都在同一温度下熔化，并且转变宽度大大减小，仅反映了熔化协同性的与序列无关的成分。在此类添加剂浓度更高的情况下，富含 dG·dC 的 DNA 在比富含 dA·dT 的分子更低的温度下熔化。圆二色光谱表明，这些添加剂在室温下对 DNA 双螺旋结构的改变非常小。使用与四烷基铵离子相关的几种小添加剂研究了这种对螺旋稳定性的差异（碱基特异性）影响。大于四乙铵离子的添加剂对螺旋稳定性影响很小。离子与 dA·dT 碱基对的优先结合需要适合 DNA“凹槽”，这与这些数据和平衡结合研究一致。这些差异效应可以与一般的不稳定效应区分开来，后者独立于大分子构象或化学的特定特征。讨论了利用这种能力改变 DNA 螺旋稳定性的碱基组成依赖性成分的可能的实验用途，以及这种现象为 dA·dT 和 dG·dC 碱基对差异稳定性的分子基础提供的见解。
Several small alkylammonium ions can eliminate, or even reverse, the usual dependence of the DNA transition temperature on base composition. For example, in 3 M tetramethylammonium chloride, or 2.4 M tetraethylammonium chloride, DNAs of different base compositions all melt at a common temperature, and with a greatly decreased breadth of transition reflecting only the sequence-independent components of melting cooperativity. At still higher concentrations of such additives, dG·dC-rich DNAs melt at lower temperatures than dA·dT-rich molecules. Circular dichroism spectra show that these additives alter the structure of the DNA double helix very little at room temperature. This differential (base-specific) effect on helix stability is investigated with several small additives related to the tetraalkylammonium ions. Additives larger than tetraethylammonium ion have little differential effect on helix stability. Preferential binding of ions to dA·dT base pairs, requiring fit into a “groove” of DNA, is consistent with these data and with equilibrium binding studies. These differential effects can be distinguished from general destabilizing effects, which are independent of specific features of macromolecular conformation or chemistry. Possible experimental uses of this ability to alter the base-composition-dependent components of the stability of the DNA helix are discussed, as well as the insight this phenomenon provides into the molecular basis for the differential stability of dA·dT and dG·dC base pairs.