Radioprotection of DNA by spermine: a molecular modelling approach.
Radioprotection of DNA by spermine: a molecular modelling approach.
复制标题
精胺对 DNA 的辐射防护：一种分子建模方法。
DOI：
--
复制
发表时间：
1999
影响因子：
2.6
通讯作者：
M. Spotheim
中科院分区：
文献类型：
--
作者：
D. Sy;S. Hugot;C. Savoye;S. Ruiz;M. Charlier;M. Spotheim
目的
观察和解释精胺对DNA辐射防护的顺序依赖性。
材料和方法
用测序凝胶电泳法分析各核苷酸位点发生直链断裂(FSB)的概率。对DNA与精胺分子的络合物和弯曲的电零DNA进行了分子模拟。
结果
精胺对辐射诱导的链断裂的影响在所研究的片段上有显著差异。在低精胺浓度下，一些序列受到保护，而另一些序列则不受保护。分子模拟计算表明，大多数电负性位点位于DNA的小槽或大槽中。带正电的精胺(Z=+4)应优先与这些位点结合。当精胺结合在较小的凹槽中时，会导致辐射分解攻击部位对OH~*自由基的可及性降低。这是由于诱因的结构修改和对攻击地点的掩蔽。在主槽结合的情况下，不会降低可访问性。这种类型的结合可以解释为什么在主槽中缺乏对具有电负性位点的序列的保护。当精胺浓度较高时，该片段受到强烈的保护。观察到具有周期性分布的保护区的核小体样断裂模式。分子模型计算表明，在弯曲的电零DNA中，攻击位置的可达性也周期性地降低。
结论
考虑到DNA的静电特性，对DNA-精胺复合体进行分子模拟，可以解释实验观察到的精胺对DNA辐射敏感性的影响。
PURPOSE
To observe and explain the sequence-dependence of DNA radioprotection by spermine.
MATERIALS AND METHODS
Sequencing gel electrophoresis was used to analyse the probability of frank strand break (FSB) induction at each nucleotide site. Molecular modelling of complexes of DNA with spermine molecules and of a curved electrically null DNA has been performed.
RESULTS
The effect of spermine on radiation-induced strand breakage varied significantly along the studied fragment. At low spermine concentration, some sequences were protected while others were unprotected. Molecular modelling calculations show that the most electro-negative sites are located in the minor or in the major groove of DNA. The positively charged spermine (Z=+4) should preferentially bind to such sites. When bound in the minor groove, spermine triggers a reduction of the accessibility of radiolytic attack sites to OH* radicals. This is due to induced structural modifications and to the masking of attack sites. In the case of major groove binding, no reduction of accessibility occurs. This type of binding can explain the lack of protection of sequences with electro-negative sites in the major groove. At high spermine concentration, the fragment is strongly protected. A nucleosome-like pattern of breakage with periodically distributed regions of protection was observed. Molecular modelling calculations show that the accessibility of the attack sites in a curved electrically null DNA is also periodically reduced.
CONCLUSIONS
Molecular modelling of DNA-spermine complexes that takes into account the electrostatic properties of DNA, allows an explanation of the experimentally observed effects of spermine on DNA radiosensitivity.
登录
查看更多内容
精胺与富含 GC 的 DNA 结合：实验和理论研究。
影响因子：
3.9
作者：
Yuki,M;Grukhin,V;Lee,CS;Haworth,IS
通讯作者：
Haworth,IS
无效 DNA 中的自吸引和自然曲率。
影响因子：
4.4
作者：
Manning,GS
通讯作者：
Manning,GS
DOI：
10.1073/pnas.95.17.9738
发表时间：
1998-08-18
影响因子：
11.1
作者：
Balasubramanian, B;Pogozelski, WK;Tullius, TD
通讯作者：
Tullius, TD
DOI：
10.1080/07391102.1998.10508261
发表时间：
1998-10-01
影响因子：
4.4
作者：
Manning, GS;Ray, J
通讯作者：
Ray, J
影响因子：
3.5
作者：
RODGER, A;TAYLOR, S;HAWORTH, IS
通讯作者：
HAWORTH, IS