Charge-transport-mediated recruitment of DNA repair enzymes.
Damaged or mismatched bases in DNA can be repaired by base excision repair enzymes (BER) that replace the defective base. Although the detailed molecular structures of many BER enzymes are known, how they colocalize to lesions remains unclear. One hypothesis involves charge transport (CT) along DNA [Yavin et al., Proc. Natl. Acad. Sci. U.S.A. 102, 3546 (2005)]. In this CT mechanism, electrons are released by recently adsorbed BER enzymes and travel along the DNA. The electrons can scatter (by heterogeneities along the DNA) back to the enzyme, destabilizing and knocking it off the DNA, or they can be absorbed by nearby lesions and guanine radicals. We develop a stochastic model to describe the electron dynamics and compute probabilities of electron capture by guanine radicals and repair enzymes. We also calculate first passage times of electron return and ensemble average these results over guanine radical distributions. Our statistical results provide the rules that enable us to perform implicit-electron Monte Carlo simulations of repair enzyme binding and redistribution near lesions. When lesions are electron absorbing, we show that the CT mechanism suppresses wasteful buildup of enzymes along intact portions of the DNA, maximizing enzyme concentration near lesions.
Fok
Pak-Wing
PW
Applied and Computational Mathematics, California Institute of Technology, Pasadena, California 91125, USA. pakwing@caltech.edu
Guo
Chin-Lin
CL
Chou
Tom
T
D000042:Absorption; D000327:Adsorption; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage; D045643:DNA Repair Enzymes / Q000378:metabolism*; D004579:Electron Transport; D004583:Electrons; D008954:Models, Biological; D009010:Monte Carlo Method; D011336:Probability; D013269:Stochastic Processes; D013997:Time Factors
D004247:DNA; D045643:DNA Repair Enzymes