The recombinase protein is a torque sensitive molecular switch

TL;DR

This study uses torque-sensitive magnetic tweezers to measure the free-energy landscape of human Recombinase hRad51 on DNA, modeling it as an out-of-equilibrium two-state system to understand its role in homologous recombination.

Contribution

It provides a thermodynamical model of hRad51/DNA interactions and proposes a mechanism for sequence discrimination during homologous recombination.

Findings

Recombinase hRad51 acts as a torque-sensitive molecular switch.

The hRad51/DNA complex can be modeled as an out-of-equilibrium two-state system.

A thermodynamical description of homologous recombination is proposed.

Abstract

How a nano-searcher finds its nano-target is a general problem in non-equilibrium statistical physics. It becomes vital when the searcher is a damaged DNA fragment trying to find its counterpart on the intact homologous chromosome. If the two copies are paired, that intact homologous sequence serves as a template to reconstitute the damaged DNA sequence, enabling the cell to survive without genetic mutations. To succeed, the search must stop only when the perfect homology is found. The biological process that ensures such a genomic integrity is called Homologous Recombination and is promoted by the Recombinase proteins. In this article, we use torque-sensitive magnetic tweezers to measure the free-energy landscape of the human Recombinase hRad51 protein assembled a DNA fragment. Based on our measurements we model the hRad51/DNA complex as an out-of-equilibrium two-state system and provide a thermodynamical description of Homologous Recombination. With this dynamical two-state model, we suggest a mechanism by which the recombinase proteins discriminate between homologous and a non-homologous sequences.