DNA Mechanical Strain Steers Transcription Factor Recognition

Mechanistic analyses integrating PIC-NIC maps with newly determined TF–DNA structures, structural comparisons, binding kinetics, and molecular simulations show that sensitive positions often coincide with strain-adapted DNA geometries, including Hoogsteen conformations, whose relaxation can enhance binding or rewire sequence specificity. Genomic single-strand breaks and repair maps further suggest that TF retention at nicked DNA may influence local repair-factor accessibility.

Together, these findings systematically map DNA backbone mechanics as a position-resolved layer of TF recognition across diverse protein families, showing how this layer can reshape binding specificity and may influence repair-factor accessibility.