Solution structure of the Dickerson DNA dodecamer containing a single ribonucleotide.
Solution structure of the Dickerson DNA dodecamer containing a single ribonucleotide.
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DOI：
10.1021/bi201710q
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发表时间：
2012-03-27
期刊：
影响因子：
2.9
通讯作者：
London, Robert E.
中科院分区：
文献类型：
--
作者：
DeRose, Eugene F.;Perera, Lalith;Murray, Michael S.;Kunkel, Thomas A.;London, Robert E.
核糖核苷酸在复制过程中经常掺入DNA中。它们被几种细胞酶识别和加工，并且它们在酵母核基因组中的持续存在导致复制应激和基因组不稳定。因此，了解核苷酸掺入对DNA结构的影响是很重要的。为了实现这一目标，在这里，我们描述的NMR结构的自互补迪克森十二聚体序列[d（CGC）rGd（AATTCGCG）]2含有两个对称定位的核糖鸟苷。不存在可观察到的H1-H2标量偶联相互作用表明核糖的C3 '-内切构象。由核糖核苷酸的存在引起的较长范围的结构扰动仅限于相邻的和反式螺旋核苷酸，而整体B型DNA结构得以维持。由于晶体学研究表明，孤立的核糖核苷酸促进全球B→A转换，我们还进行了分子建模分析，以评估更高的核糖核苷酸取代水平的结构后果。增加核糖核苷酸含量使小沟宽度增加到更类似于A-DNA的值，但即使50%的核糖核苷酸取代也不能完全将B-DNA转化为A-DNA。将本结构与RNA酶H2结合的DNA的结构进行比较，支持这样的结论，即与其他DNA-蛋白质复合物一样，DNA构象受到与蛋白质相互作用的强烈影响。
Ribonucleotides are frequently incorporated into DNA during replication. They are recognized and processed by several cellular enzymes, and their continued presence in the yeast nuclear genome results in replicative stress and genome instability. Thus, it is important to understand the effects of isolated ribonucleotide incorporation on DNA structure. Towards this goal, here we describe the NMR structure of the self-complementary Dickson dodecamer sequence [d(CGC)rGd(AATTCGCG)]2 containing two symmetrically positioned riboguanosines. The absence of an observable H1-H2 scalar coupling interaction indicates a C3'-endo conformation for the ribose. Longer-range structural perturbations resulting from the presence of the ribonucleotide are limited to the adjacent and trans-helical nucleotides, while the global B-form DNA structure is maintained. Since crystallographic studies have indicated that isolated ribonucleotides promote global B→A transitions, we also performed molecular modeling analyses to evaluate the structural consequences of higher ribonucleotide substitution levels. Increasing the ribonucleotide content increased the minor groove width toward values more similar to A-DNA, but even 50% ribonucleotide substitution did not fully convert the B-DNA to A-DNA. Comparing the present structure with the structure of an RNase H2-bound DNA supports the conclusion that, as with other DNA-protein complexes, the DNA conformation is strongly influenced by the interaction with the protein.
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