碱基对错配可通过协同扭结使小DNA环不稳定
Base-pair mismatch can destabilize small DNA loops through cooperative kinking
摘要：
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（FRET），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，尽管降低了整体弯曲应力，但错配降低了环的寿命，并且当错配被放置在DNA中点时，降低最大。这些发现表明，碱基对错配通过称为合作扭结的变构机制将弯曲应力转移到环的相对侧。基于这一机制，我们提出了一个三态模型，解释了DNA环的热力学和动力学稳定性之间的明显二分法。
英文摘要：
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 (FRET), we measured the lifetimes of tightly bent DNA loops with and without base pair mismatch. Surprisingly, for loops captured by stackable sticky ends, 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 show that base pair mismatch transfers bending stress to 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 of DNA loops.
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