Accelerated search kinetics mediated by redox reactions of DNA repair enzymes

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.

💡 Research Summary

The paper presents a quantitative theoretical framework for the “charge‑transport” (CT) hypothesis that has been proposed to explain how base‑excision‑repair (BER) enzymes locate DNA lesions more efficiently than would be expected from simple diffusion and sliding alone. The hypothesis, originally articulated in experimental work by Yavin and colleagues (PNAS 2005), posits that BER enzymes containing iron‑sulfur (