High-Fidelity DNA Sensing by Protein Binding Fluctuations

TL;DR

This paper demonstrates how RecA protein binding fluctuations enable high-fidelity DNA length sensing, with enhanced discrimination due to ATP-driven out-of-equilibrium dynamics, modeled as a generalized kinetic proofreading mechanism.

Contribution

It introduces a model explaining DNA length sensing via out-of-equilibrium binding fluctuations, extending kinetic proofreading concepts to biological DNA-protein interactions.

Findings

Enhanced DNA length discrimination with ATP consumption

Binding fluctuations resemble microtubule instability

Multistage irreversible pathways improve sensing precision

Abstract

One of the major functions of RecA protein in the cell is to bind single-stranded DNA exposed upon damage, thereby triggering the SOS repair response.We present fluorescence anisotropy measurements at the binding onset, showing enhanced DNA length discrimination induced by adenosine triphosphate consumption. Our model explains the observed DNA length sensing as an outcome of out-of equilibrium binding fluctuations, reminiscent of microtubule dynamic instability. The cascade architecture of the binding fluctuations is a generalization of the kinetic proofreading mechanism. Enhancement of precision by an irreversible multistage pathway is a possible design principle in the noisy biological environment.