Kühner Ferdinand, Morfill Julia, Neher Richard A, Blank Kerstin, Gaub Hermann E
Center for NanoScience, Ludwig-Maximilians Universität München, Munich, Germany.
Biophys J. 2007 Apr 1;92(7):2491-7. doi: 10.1529/biophysj.106.095836. Epub 2007 Jan 11.
DNA containing repetitive sequences displays richer dynamics than heterogeneous sequences. In the genome the number of repeat units of repetitive sequences, known as microsatellites, may vary during replication by DNA slippage and their expansion gives rise to serious disorders. We studied the mechanical properties of repetitive DNA using dynamic force spectroscopy and found striking differences compared with ordinary heterogeneous sequences. Repetitive sequences dissociate at lower forces and elongate above a certain threshold force. This yield force was found to be rate dependent. Following the rapid stretching of the DNA duplex, the applied force relaxes by stepwise elongation of this duplex. Conversely, contraction of the DNA duplex can be observed at low forces. The stepwise elongation and shortening is initiated by single slippage events, and single-molecule experiments might help to explain the molecular mechanisms of microsatellites formation. In addition to the biological importance, the remarkable properties of repetitive DNA can be useful for different nanomechanical applications.
含有重复序列的DNA比异质序列表现出更丰富的动力学特性。在基因组中,被称为微卫星的重复序列的重复单元数量在复制过程中可能因DNA滑动而发生变化,其扩增会引发严重疾病。我们使用动态力谱研究了重复DNA的力学性质,发现与普通异质序列相比存在显著差异。重复序列在较低力的作用下解链,并在超过一定阈值力时伸长。发现这种屈服力与速率有关。在DNA双链快速拉伸后,施加的力通过该双链的逐步伸长而松弛。相反,在低力作用下可以观察到DNA双链的收缩。逐步伸长和缩短是由单个滑动事件引发的,单分子实验可能有助于解释微卫星形成的分子机制。除了生物学重要性外,重复DNA的显著特性可用于不同的纳米机械应用。