Accelerated Target Selection By Repair Enzymes Through Charge Transport

Abstract

A Charge Transport (CT) mechanism has been proposed in several papers (for example see Yavin et al. PNAS 102, 3546 (2005)) to explain the co-localization of Base Excision Repair (BER) enzymes to lesions (damaged bases) on DNA. The CT mechanism relies on the presence of iron-sulfur clusters on the enzymes; these clusters can undergo redox reactions to modify the enzymes’ binding affinity. The redox reactions are mediated by the DNA strand and involve the exchange of electrons between individual BER enzymes. This process effectively increases the desorption rate of enzymes to promote their redistribution and co-localization to lesions.We study the search times of BER enzymes to lesions by using a mass action model of enzyme dynamics and electron transport. We show that when the enzyme copy number is small, the CT mechanism reduces the search time of otherwise “passive” enzymes that simply attach to the DNA without desorbing. Other physical effects in our enzyme model include an explicit treatment of their dynamics in solution, diffusion along the DNA and facilitated adsorption by guanine radicals.View Large Image | View Hi-Res Image | Download PowerPoint Slide