Single molecule investigation of Ag+ interactions with single cytosine-, methylcytosine- and hydroxymethylcytosine-cytosine mismatches in a nanopore.
Single molecule investigation of Ag+ interactions with single cytosine-, methylcytosine- and hydroxymethylcytosine-cytosine mismatches in a nanopore.
复制标题
DOI：
10.1038/srep05883
复制
发表时间：
2014-08-08
影响因子：
4.6
通讯作者：
Gu LQ
中科院分区：
文献类型：
--
作者：
Wang Y;Luan BQ;Yang Z;Zhang X;Ritzo B;Gates K;Gu LQ
胞嘧啶-Ag-胞嘧啶相互作用和DNA双链体中的胞嘧啶修饰引起了人们极大的研究兴趣。胞嘧啶（C）修饰，如甲基胞嘧啶（mC）和羟甲基胞嘧啶（hmC）与肿瘤发生有关。然而，直接区分C，mC和hmC碱基而不标记，修饰和扩增的方法仍然缺失。此外，Ag+与胞嘧啶-胞嘧啶（C-C）错配的配位性质还不清楚。利用α-溶血素纳米孔，我们表明在Ag+存在下，胞嘧啶-胞嘧啶（C-C）对的双链体稳定性增加最多，其次是胞嘧啶-甲基胞嘧啶（C-mC）对和胞嘧啶-羟甲基胞嘧啶（C-hmC）对，其没有可观察到的Ag+诱导的稳定。分子动力学模拟表明，氢键介导的配对的C-C错配的结果在Ag+的结合位点。胞嘧啶修饰（如mC和hmC）破坏氢键，导致Ag+结合位点的破坏。我们的实验方法为研究金属离子与DNA的相互作用提供了一个新的平台，也可以作为核碱基修饰的直接检测方法。
Both cytosine-Ag-cytosine interactions and cytosine modifications in a DNA duplex have attracted great interest for research. Cytosine (C) modifications such as methylcytosine (mC) and hydroxymethylcytosine (hmC) are associated with tumorigenesis. However, a method for directly discriminating C, mC and hmC bases without labeling, modification and amplification is still missing. Additionally, the nature of coordination of Ag+ with cytosine-cytosine (C-C) mismatches is not clearly understood. Utilizing the alpha-hemolysin nanopore, we show that in the presence of Ag+, duplex stability is most increased for the cytosine-cytosine (C-C) pair, followed by the cytosine-methylcytosine (C-mC) pair, and the cytosine-hydroxymethylcytosine (C-hmC) pair, which has no observable Ag+ induced stabilization. Molecular dynamics simulations reveal that the hydrogen-bond-mediated paring of a C-C mismatch results in a binding site for Ag+. Cytosine modifications (such as mC and hmC) disrupted the hydrogen bond, resulting in disruption of the Ag+ binding site. Our experimental method provides a novel platform to study the metal ion-DNA interactions and could also serve as a direct detection method for nucleobase modifications.
登录
查看更多内容
影响因子：
3.3
作者：
de Zoysa, Ranulu Samanthi S.;Jayawardhana, Dilani A.;Guan, Xiyun
通讯作者：
Guan, Xiyun
影响因子：
4.6
作者：
KISTENMACHER, TJ;ROSSI, M;MARZILLI, LG
通讯作者：
MARZILLI, LG
影响因子：
4.9
作者：
Lin, Yen-Hsiu;Tseng, Wei-Lung
通讯作者：
Tseng, Wei-Lung
影响因子：
4.4
作者：
JORGENSEN, WL;CHANDRASEKHAR, J;KLEIN, ML
通讯作者：
KLEIN, ML
影响因子：
15
作者：
Atwell, S;Meggers, E;Schultz, PG
通讯作者：
Schultz, PG