Georghiou S, Kubala S M, Large C C
Department of Physics, University of Tennessee, Knoxville 37996-1200, USA.
Photochem Photobiol. 1998 May;67(5):526-31.
The deformability of DNA is of crucial importance in a number of processes and interactions, such as its enzymatic recognition, its packaging into chromosomes, its interactions with drugs, and the formation of photodimers in it. Here we have studied this property by following the formation of excited-state molecular complexes (excimers) between adjacent bases of poly(dA-dT).poly(dA-dT) at 20 degrees C. The force that drives the helix distortion appears to stem mainly from charge-resonance interaction. The results indicate that the deformability of the helix on the nanosecond time scale is considerable at normal solvent viscosities, whereas it is greatly reduced by frictional forces at high viscosities (attained through sucrose addition) at which the excimer has a much less favorable geometry: the difference in the interaction energies between 1 cP and 58 cP is about 6 kcal/mol, a value that is similar to the base stacking energies for the undistorted helix. This behavior parallels the modulation by the solvent viscosity of the thermally driven motions of the bases of poly(dA).poly(dT), which we recently reported on the basis of time-resolved intrinsic fluorescence anisotropy measurements (S. Georghiou et al., Biophys, J., 70, 1909-1922, 1996). It is inferred that environmental impediments to molecular motion can modulate the conformation and dynamics of DNA. Such modulation might play a role in gene regulation: particular base configurations, which can be enzymatically recognized, may be attained as dictated by the prevailing viscosity conditions and/or geometric constraints. By contrast, up to 3 M NaCl or 0.1 M MgCl2 do not significantly reduce the deformability of the helix. The considerable plasticity of this polynucleotide is probably linked to the significant flexibility of the TA step that may account for the wide-spread use of the TATA sequence in transcription, site-specific recombination and the initiation of DNA replication.
DNA的可变形性在许多过程和相互作用中至关重要，例如其酶促识别、包装成染色体、与药物的相互作用以及其中光二聚体的形成。在这里，我们通过跟踪20摄氏度下聚（dA-dT）·聚（dA-dT）相邻碱基之间激发态分子复合物（激基缔合物）的形成来研究这一性质。驱动螺旋扭曲的力似乎主要源于电荷共振相互作用。结果表明，在正常溶剂粘度下，螺旋在纳秒时间尺度上的可变形性相当大，而在高粘度（通过添加蔗糖实现）下，摩擦力会大大降低这种可变形性，此时激基缔合物的几何形状不太有利：1厘泊和58厘泊之间相互作用能的差异约为6千卡/摩尔，这一数值与未扭曲螺旋的碱基堆积能相似。这种行为与我们最近基于时间分辨固有荧光 anisotropy 测量报道的聚（dA）·聚（dT）碱基热驱动运动受溶剂粘度调制的情况相似（S. Georghiou等人，《生物物理杂志》，70，1909 - 1922，1996）。据推测，分子运动的环境阻碍可以调节DNA的构象和动力学。这种调节可能在基因调控中起作用：特定的碱基构型可以被酶识别，可能会根据当前的粘度条件和/或几何约束而达到。相比之下，高达3 M的NaCl或0.1 M的MgCl2不会显著降低螺旋的可变形性。这种多核苷酸的显著可塑性可能与TA步的显著灵活性有关，这可能解释了TATA序列在转录、位点特异性重组和DNA复制起始中的广泛应用。
