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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 BaseExcision Repair (BER) enzymes to lesions on DNA. The CT mechanism relies onredox reactions of iron-sulfur cofactors that modify the enzyme's bindingaffinity. These redox reactions are mediated by the DNA strand and involve theexchange of electrons between BER enzymes along DNA. We propose a mathematicalmodel that incorporates enzyme binding/unbinding, electron transport, andenzyme diffusion along DNA. Analysis of our model within a range of parametervalues suggests that the redox reactions can increase desorption of BER enzymesnot already bound to their targets, allowing the enzymes to be recycled, thusaccelerating the overall search process. This acceleration mechanism is mosteffective when enzyme copy numbers and enzyme diffusivity along the DNA aresmall. Under such conditions, we find that CT BER enzymes find their targetsmore quickly than simple "passive" enzymes that simply attach to the DNAwithout desorbing.

Accelerated search kinetics mediated by redox reactions of DNA repair enzymes