A common rule for the intermediate state caused by DNA mismatch in single-molecule experiments
A common rule for the intermediate state caused by DNA mismatch in single-molecule experiments
复制标题
单分子实验中DNA错配引起的中间态的通用规律
DOI：
10.1088/1572-9494/acc64c
复制
发表时间：
2023-03
期刊：
影响因子：
--
通讯作者：
Yanghui Liu
中科院分区：
文献类型：
--
作者：
Xiaoya Song;Chao Yang;Yuyu Feng;Hu Chen;Yanghui Liu
DNA结构缺陷，如DNA错配，在某些生物过程中经常发生。它们难以识别，最近成为单分子研究的焦点。为了检测DNA错配对DNA发夹稳定性的影响，我们先后进行了3次单分子实验。然而，对于DNA错配引起的中间状态的结果，并没有达成共识。基于扩展的ox-DNA模型，将DNA错配引入不同茎长（12 ~ 20 bps）和4T的DNA发夹的茎中。系统地研究了发夹环的中间状态及其与DNA错配位置的关系。结果表明，DNA错配明显降低了DNA发夹的临界力。同时，在DNA错配位置的相位空间中构造相图，推广了中间态与DNA错配位置相关的一般规律。其对角线上的三个片段分别对应DNA错配的比例位置范围[0,0.55]、[0.55,0.85]和[0.85,1]。在[0.55,0.85]范围内，DNA发夹的延伸概率分布为展开、中间和折叠态。而在其他范围[0,0.55]和[0.85,1]，扩展概率分布为展开和折叠状态。三个单分子实验中使用的DNA发夹的DNA错配比例位置（0.65,0.4736,0.5）分别落在[0.55,0.85]和[0,0.55]范围内。显然，在相图中推广的共同规律不仅澄清了三个单分子实验之间的不一致，而且突出了今后单分子实验的设计。
Defective structures, such as DNA mismatches, occur in DNA with a high frequency in some biological processes. They are difficult to identify and have recently become the focus of single-molecule investigations. Three single-molecule experiments were successively conducted to detect the effects of DNA mismatch on the stability of DNA hairpins. However, there was no consensus regarding the results of the intermediate state caused by DNA mismatch. Based on the extended ox-DNA model, DNA mismatch was introduced to the stem of DNA hairpins with different stem lengths (12–20 bps) and 4T in hairpin loops. The intermediate state and its dependence on the position of the DNA mismatch in the stem from the hairpin loop were systematically studied. The results indicated that DNA mismatch definitely reduced the critical forces of DNA hairpins. At the same time, a common rule about the dependence of the intermediate state on the position of DNA mismatch was generalized in a phase diagram constructed in a phase space of a scaled position of DNA mismatch. Three segments on its diagonal line corresponded to the ranges of the scaled position of DNA mismatch [0, 0.55), [0.55, 0.85), and [0.85, 1], respectively. In the [0.55, 0.85) range, the extension probability distribution of DNA hairpins had unfolded, intermediate, and folded states. In contrast, in the other ranges [0, 0.55) and [0.85, 1], the extension probability distributions had unfolded and folded states. The scaled positions of DNA mismatch for the DNA hairpins used in the three single-molecule experiments (0.65, 0.4736, and 0.5) fell in the ranges [0.55, 0.85) and [0, 0.55). Obviously, the common rule generalized in the phase diagram not only clarifies the non-consensus between the three single-molecule experiments but also highlights the design of single-molecule experiments in the future.
登录
查看更多内容
影响因子：
56.9
作者：
Onoa, B;Dumont, S;Bustamante, C
通讯作者：
Bustamante, C
影响因子：
56.9
作者：
Woodside, Michael T.;Anthony, Peter C.;Block, Steven M.
通讯作者：
Block, Steven M.
影响因子：
3.8
作者：
Leon-Ortiz, Ana Maria;Svendsen, Jennifer;Boulton, Simon J.
通讯作者：
Boulton, Simon J.
影响因子：
8.6
作者：
Neupane, Krishna;Hoffer, Noel Q.;Woodside, M. T.
通讯作者：
Woodside, M. T.
影响因子：
4.1
作者：
R. M. Wadkins
通讯作者：
R. M. Wadkins