DNA Internal Motion Likely Accelerates Protein Target Search in a Packed Nucleoid

Transcription factors must diffuse through densely packed and coiled DNA to find their binding sites. Using a coarse-grained model of DNA and lac repressor (LacI) in the Escherichia coli nucleoid, simulations were performed to examine how LacI diffuses in such a space. Despite the canonical picture of LacI diffusing rather freely, in reality the DNA is densely packed, is not rigid but highly mobile, and the dynamics of DNA dictates to a great extent the LacI motion. A possibly better picture of unbound LacI motion is that of gated diffusion, where DNA confines LacI in a cage, but LacI can move between cages when hindering DNA strands move out of the way.

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