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Accelerated search kinetics mediated by redox reactions of DNA repair enzymes

Fok, Pak-Wing and Chou, Tom (2009) Accelerated search kinetics mediated by redox reactions of DNA repair enzymes. Biophysical Journal, 96 (10). pp. 3949-3958. ISSN 0006-3495. PMCID PMC2712205.

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A charge transport (CT) mechanism has been proposed in several articles 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 lesions, 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.

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Fok, Pak-Wing0000-0001-9655-614X
Additional Information:© 2009 Biophysical Society. Submitted December 15, 2008, and accepted for publication February 11, 2009. P.-W. Fok is grateful for helpful discussions with A. K. Boal and J. Geneveaux. The authors acknowledge support from the National Science Foundation (DMS-0349195) and the National Institutes of Health (K25AI058672).
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Issue or Number:10
PubMed Central ID:PMC2712205
Record Number:CaltechAUTHORS:20090727-152820676
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:14683
Deposited By: Jason Perez
Deposited On:07 Aug 2009 22:55
Last Modified:03 Oct 2019 00:51

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