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Force-Induced DNA Slippage

Ferdinand Kühner ^*, Julia Morfill ^*, Richard A. Neher , Kerstin Blank ^* and Hermann E. Gaub ^*

^* Chair for Applied Physics and Center for NanoScience, and Arnold Sommerfeld Center for Theoretical Physics and Center for Nanoscience, Ludwig-Maximilians Universität München, Munich, Germany

Correspondence: Address reprint requests to Ferdinand Kühner, E-mail: ferdinand.kuehner{at}physik.uni-muenchen.de.

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.

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