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Updated: Jun 6, 2025

Author Spotlight: Characterizing DNA Replication of Pathogenic Repeats to Uncover Mechanisms of Replication Fork Stalling and Expansion
Published on: September 13, 2024
Mechanical causes and implications of repetitive DNA motifs
1Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, USA; Department of Civil and Environmental Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
Abstract:
Experimental research suggests that local patterns in DNA sequences can result in stiffer or more curved structures, potentially impacting chromatin formation, transcription regulation, and other processes. However, the effect of sequence variation on DNA geometry and mechanics remains relatively underexplored. Using rigid base pair models to aid rapid computation, we investigated the sample space of 100 bp DNA sequences to identify mechanical extrema based on metrics such as static persistence length, global bend, or angular deviation. Our results show that repetitive DNA motifs are overrepresented in these extrema. We identified specific extremal motifs and demonstrated that their geometric and mechanical properties significantly differ from standard DNA through hierarchical clustering. We provide a mathematical argument supporting the presence of DNA repeats in extremizing sequences. Finally, we find that repetitive DNA motifs with extreme mechanical properties are prevalent in genetic databases and hypothesize that their unique mechanical properties could contribute to this abundance.
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