Kinetic FRG Young Researchers Workshop
March 2-5, 2009
CSIC Building (#406),
Seminar Room 4122.
Directions: home.cscamm.umd.edu/directions
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Accelerated DNA Repair by Charge Transport: Stochastic Analysis and Deterministic Models
Dr. Pak-Wing Fok
California Institute of Technology and UCLA
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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 colocalization of Base Excision Repair enzymes to lesions on DNA. The CT mechanism relies on redox reactions of iron-sulfur cofactors on the enzyme. Electrons are released by recently adsorbed enzymes and travel along the DNA. The electrons can scatter back to the enzyme to destabilize it and knock it off the strand, or they can be absorbed by nearby lesions and guanine radicals.
I will first present a stochastic description for the electron dynamics in a discrete model of CT-mediated enzyme kinetics. By calculating the enzyme adsorption/desorption probabilities, I develop an implicit electron Monte Carlo scheme and use it to simulate the build-up of enzyme density along a DNA strand. Then, I will present a Partial Differential Equation (PDE) model for CT-mediated enzyme binding, desorption and redistribution. The model incorporates the effect of finite enzyme copy number, enzyme diffusion along DNA and a mean field description of electron dynamics. By computing the flux of enzymes into a lesion, the search time for an enzyme to find a lesion can be estimated. The results show that the CT mechanism can significantly accelerate the search of repair enzymes.
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