The search kinetics of a target inside the cell nucleus

TL;DR

This paper models the search process of transcription factors within the cell nucleus, providing analytical estimates for binding and diffusion times, and showing how DNA density influences search efficiency.

Contribution

The study introduces new analytical expressions for search times considering switching between DNA-bound and free diffusion, aligning with experimental data.

Findings

The mean DNA binding time is approximately 3.7 times the free diffusion time for Lac-I TF.

The derived formulas match observed data for target binding times.

Higher DNA density enhances the efficiency of the search process.

Abstract

The mean time required by a transcription factor (TF) or an enzyme to find a target in the nucleus is of prime importance for the initialization of transcription, gene activation or the start of DNA repair. We obtain new estimates for the mean search time when the TF or enzyme, confined to the cell nucleus, can switch from a one dimensional motion along the DNA and a free Brownian regime inside the crowded nucleus. We give analytical expressions for the mean time the particle stays bound to the DNA, $\tau_{DNA}$, and the mean time it diffuses freely, $\tau_{free}$. Contrary to previous results but in agreement with experimental data, we find a factor $\tau_{DNA} \approx 3.7 \tau_{free}$ for the Lac-I TF. The formula obtained for the time required to bind to a target site is found to be coherent with observed data. We also conclude that a higher DNA density leads to a more efficient search process.