Environmental control of the deformability of the DNA double helix

被引:16
作者
Georghiou, S [1 ]
Kubala, SM [1 ]
Large, CC [1 ]
机构
[1] Univ Tennessee, Dept Phys, Lab Mol Biophys, Knoxville, TN 37996 USA
关键词
D O I
10.1111/j.1751-1097.1998.tb09088.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 widespread use of the TATA sequence in transcription, site-specific recombination and the initiation of DNA replication.
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页码:526 / 531
页数:6
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