不寻常的螺旋包装在含有突变热点的DNA晶体中
Y Timsit1, E Westhof, R P Fuchs
1Institut de Biologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique, Strasbourg, France.
Nature
|October 5, 1989
概括
化学致癌物诱导在NarI部位的移突变. DNA结构分析揭示了G-C基对开放和新型包装,解释了变种机制,并为DNA相互作用提供了模型.
科学领域:
- 分子生物学分子生物学
- 结构生物学 结构生物学
- 化学致癌发生的原因
背景情况:
- NarI 限制酶识别部位 (GGCGCC) 是 -2 框架转移突变发生的突变热点.
- 化学致癌物,如N-2-乙氨基,诱导这些框架转移突变,特别是在NarI序列.
- 致癌物与NarI部位内的3'-最多的关氨酸残留物结合,引发了变异发生.
研究的目的:
- 为了阐明在NarI站点的框架转移突变发生的结构基础.
- 为了确定一个突变性NarI DNA序列的X射线晶体结构.
- 了解DNA序列和化学修饰如何导致结构变化和突变.
主要方法:
- 在2.8 Å分辨率的X射线晶体学.
- 选择一个非palindromic dodecamer d ((ACCGGCGCCACA) 对应的高度致变性NarI站点.
- 从正规B型中脱离DNA偏差的结构分析.
主要成果:
- 确定的DNA结构与正规的B型DNA有显著的差异.
- 观察到三个G-C基对的部分开放.
- 确定了高螺旋扭转值和依赖序列的三中心键.
- 揭示了一种涉及槽-脊柱相互作用的新型DNA螺旋包装.
- 酸盐-细胞因子相互作用与G-C基对开放有关.
结论:
- 晶体结构提供了一个分子模型,用于在NarI站点的框架转移突变.
- 特定的结构特征,包括G-C基对开放,解释了突变性潜力.
- 观察到的DNA包装提供了对DNA分子相互作用在生物过程中的见解,如重组.
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