c-MYC promoter G-quadruplex formed at the 5'-end of NHE III1 element: insights into biological relevance and parallel-stranded G-quadruplex stability.
c-MYC promoter G-quadruplex formed at the 5'-end of NHE III1 element: insights into biological relevance and parallel-stranded G-quadruplex stability.
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DOI：
10.1093/nar/gkr612
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发表时间：
2011-11-01
影响因子：
14.9
通讯作者：
Yang D
中科院分区：
文献类型：
--
作者：
Mathad RI;Hatzakis E;Dai J;Yang D
我们研究了在Myc 1234中形成的G-四链体的结构和稳定性，Myc 1234包含c-MYC启动子NHE III 1的四个连续5′运行的鸟嘌呤，最近已被证明在水溶液中的超螺旋质粒系统中形成。我们确定了1：2：1平行链环异构体的NMR溶液结构，这是Myc 1234在K+溶液中形成的两个主要环异构体之一。这种主要的环异构体，虽然共享相同的折叠结构，似乎是显着不稳定的主要环异构体中形成的单链c-MYC NHE III 1寡核苷酸，Myc 2345 G-四链体。我们的NMR结构表明，两个1：2：1平行的c-MYC G-四链体的不同的热稳定性可能是由不同的碱基构象的单核苷酸环。Myc 1234 G-四链体在超螺旋质粒中形成的观察结果表明超螺旋在启动子序列中G-四链体形成中的潜在作用。我们还进行了系统的热力学分析的修改c-MYC NHE III 1序列，这提供了定量测量的各种环序列的平行链G-四链体的热稳定性的贡献。这些信息对于理解启动子G-四链体环异构体的平衡及其药物靶向是重要的。
We studied the structures and stabilities of G-quadruplexes formed in Myc1234, the region containing the four consecutive 5′ runs of guanines of c-MYC promoter NHE III1, which have recently been shown to form in a supercoiled plasmid system in aqueous solution. We determined the NMR solution structure of the 1:2:1 parallel-stranded loop isomer, one of the two major loop isomers formed in Myc1234 in K+ solution. This major loop isomer, although sharing the same folding structure, appears to be markedly less stable than the major loop isomer formed in the single-stranded c-MYC NHE III1 oligonucleotide, the Myc2345 G-quadruplex. Our NMR structures indicated that the different thermostabilities of the two 1:2:1 parallel c-MYC G-quadruplexes are likely caused by the different base conformations of the single nucleotide loops. The observation of the formation of the Myc1234 G-quadruplex in the supercoiled plasmid thus points to the potential role of supercoiling in the G-quadruplex formation in promoter sequences. We also performed a systematic thermodynamic analysis of modified c-MYC NHE III1 sequences, which provided quantitative measure of the contributions of various loop sequences to the thermostabilities of parallel-stranded G-quadruplexes. This information is important for understanding the equilibrium of promoter G-quadruplex loop isomers and for their drug targeting.
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影响因子：
16.8
作者：
Kouzine, Fedor;Sanford, Suzanne;Levens, David
通讯作者：
Levens, David
影响因子：
64.8
作者：
NOWELL, P;FINAN, J;CROCE, CM
通讯作者：
CROCE, CM
影响因子：
4.8
作者：
Gonzalez, Veronica;Guo, Kexiao;Sun, Daekyu
通讯作者：
Sun, Daekyu
影响因子：
15
作者：
Dai, JX;Dexheimer, TS;Yang, DZ
通讯作者：
Yang, DZ
DOI：
10.1073/pnas.79.24.7824
发表时间：
1982-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
DALLAFAVERA, R;BREGNI, M;CROCE, CM
通讯作者：
CROCE, CM