Accelerated search kinetics mediated by redox reactions of DNA repair enzymes

TL;DR

This paper presents a mathematical model demonstrating that redox reactions facilitate faster DNA repair enzyme targeting by promoting enzyme recycling and diffusion, especially under conditions of low enzyme concentration and mobility.

Contribution

The study introduces a new mathematical framework showing how redox-mediated charge transport enhances DNA repair enzyme search efficiency.

Findings

Redox reactions increase enzyme desorption and recycling.

Charge transport accelerates enzyme target localization.

Effectiveness is highest at low enzyme copy numbers and diffusivity.

Abstract

A Charge Transport (CT) mechanism has been proposed in several papers (e.g., Yavin, et al. PNAS, v102 3546 (2005)) to explain the localization of Base Excision Repair (BER) enzymes to lesions on DNA. The CT mechanism relies on redox reactions of iron-sulfur cofactors that modify the enzyme's binding affinity. These redox reactions are mediated by the DNA strand and involve the exchange of electrons between BER enzymes along DNA. We propose a mathematical model that incorporates enzyme binding/unbinding, electron transport, and enzyme diffusion along DNA. Analysis of our model within a range of parameter values suggests that the redox reactions can increase desorption of BER enzymes not already bound to their targets, allowing the enzymes to be recycled, thus accelerating the overall search process. This acceleration mechanism is most effective when enzyme copy numbers and enzyme diffusivity along the DNA are small. Under such conditions, we find that CT BER enzymes find their targets more quickly than simple "passive" enzymes that simply attach to the DNA without desorbing.