Base-Pair Mismatch Can Destabilize Small DNA Loops through Cooperative Kinking.
Base-Pair Mismatch Can Destabilize Small DNA Loops through Cooperative Kinking.
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DOI：
10.1103/physrevlett.122.218101
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发表时间：
2019-05-31
影响因子：
8.6
通讯作者：
Kim HD
中科院分区：
文献类型：
--
作者：
Jeong J;Kim HD
碱基对错配可以缓解高应变DNA分子中的机械应力，但它如何影响其动力学稳定性尚不清楚。使用单分子荧光共振能量转移，我们测量了有和没有碱基对错配的紧密弯曲的DNA环的寿命。令人惊讶的是，对于由可堆叠的粘性末端捕获的环，其在退火时留下单链DNA断裂（或切口），尽管降低了整体弯曲应力，但错配降低了环寿命，并且当错配被放置在DNA中点时，降低最大。这些发现表明，碱基对错配增加弯曲应力在另一侧的环通过变构机制被称为合作扭结。基于这种机制，我们提出了一个三态模型，解释热力学和动力学稳定性之间的明显二分法。
Base-pair mismatch can relieve mechanical stress in highly strained DNA molecules, but how it affects their kinetic stability is not known. Using single-molecule fluorescence resonance energy transfer, we measured the lifetimes of tightly bent DNA loops with and without base-pair mismatch. Surprisingly, for loops captured by stackable sticky ends which leave single-stranded DNA breaks (or nicks) upon annealing, the mismatch decreased the loop lifetime despite reducing the overall bending stress, and the decrease was largest when the mismatch was placed at the DNA midpoint. These findings suggest that base-pair mismatch increases bending stress at the opposite side of the loop through an allosteric mechanism known as cooperative kinking. Based on this mechanism, we present a three-state model that explains the apparent dichotomy between thermodynamic and kinetic stability.