Charge-transport-mediated recruitment of DNA repair enzymes.

Content Provider	Europe PMC
Author	Fok, Pak-Wing Guo, Chin-Lin Chou, Tom
Copyright Year	2008
Abstract	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.
Related Links	https://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC2671188&blobtype=pdf
ISSN	00219606
Volume Number	129
DOI	10.1063/1.3026735
PubMed Central reference number	PMC2671188
Issue Number	23
PubMed reference number	19102557
Journal	The Journal of Chemical Physics [J Chem Phys]
e-ISSN	10897690
Language	English
Publisher	American Institute of Physics
Publisher Date	2008-12-01
Access Restriction	Open
Rights License	Copyright © 2008 American Institute of Physics
Content Type	Text
Resource Type	Article
Subject	Physics and Astronomy Medicine Physical and Theoretical Chemistry