Effects of intersegmental transfers on target location by proteins

TL;DR

This study models how proteins locate targets on DNA via facilitated diffusion, highlighting the significant role of intersegmental transfer in reducing search time and increasing robustness, with implications for understanding protein-DNA interactions.

Contribution

It introduces a comprehensive model including intersegmental transfer, revealing its impact on search efficiency and optimal conditions, which was not addressed in previous models.

Findings

Intersegmental transfer reduces search time significantly.

Including intersegmental transfer increases robustness to parameter variations.

Optimal search occurs in regimes different from models without intersegmental transfer.

Abstract

We study a model for a protein searching for a target, using facilitated diffusion, on a DNA molecule confined in a finite volume. The model includes three distinct pathways for facilitated diffusion: (a) sliding - in which the protein diffuses along the contour of the DNA (b) jumping - where the protein travels between two sites along the DNA by three-dimensional diffusion, and finally (c) intersegmental transfer - which allows the protein to move from one site to another by transiently binding both at the same time. The typical search time is calculated using scaling arguments which are verified numerically. Our results suggest that the inclusion of intersegmental transfer (i) decreases the search time considerably (ii) makes the search time much more robust to variations in the parameters of the model and (iii) that the optimal search time occurs in a regime very different than that found for models which ignore intersegmental transfers. The behavior we find is rich and shows surprising dependencies, for example, on the DNA length.