RecA-mediated homology search as a nearly optimal signal detection system

TL;DR

This paper models RecA-mediated DNA homology search as a signal detection problem, revealing that its binding energetics are nearly optimal for sequence recognition, and suggests deformation enhances detection.

Contribution

It introduces a signal detection framework to analyze RecA-DNA interactions, showing their near-optimality and proposing a role for DNA deformation in recognition.

Findings

RecA-DNA binding energy is nearly optimal for homology detection.

Deformation of DNA by RecA enhances the recognition process.

The signal detection model can evaluate other molecular recognition systems.

Abstract

Homologous recombination facilitates the exchange of genetic material between homologous DNA molecules. This crucial process requires detecting a specific homologous DNA sequence within a huge variety of heterologous sequences. The detection is mediated by RecA in E. coli, or members of its superfamily in other organisms. Here we examine how well is the RecA-DNA interaction adjusted to its task. By formulating the DNA recognition process as a signal detection problem, we find the optimal value of binding energy that maximizes the ability to detect homologous sequences. We show that the experimentally observed binding energy is nearly optimal. This implies that the RecA-induced deformation and the binding energetics are fine-tuned to ensure optimal sequence detection. Our analysis suggests a possible role for DNA extension by RecA, in which deformation enhances detection. The present signal detection approach provides a general recipe for testing the optimality of other molecular recognition systems.