CaltechAUTHORS
  A Caltech Library Service

Charge-transport-mediated recruitment of DNA repair enzymes

Fok, Pak-Wing and Guo, Chin-Lin and Chou, Tom (2008) Charge-transport-mediated recruitment of DNA repair enzymes. Journal of Chemical Physics, 129 (23). Art. No. 235101. ISSN 0021-9606. http://resolver.caltech.edu/CaltechAUTHORS:FOKjcp08

[img]
Preview
PDF - Published Version
See Usage Policy.

348Kb

Use this Persistent URL to link to this item: http://resolver.caltech.edu/CaltechAUTHORS:FOKjcp08

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.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1063/1.3026735DOIArticle
http://link.aip.org/link/?JCPSA6/129/235101/1PublisherArticle
ORCID:
AuthorORCID
Fok, Pak-Wing0000-0001-9655-614X
Additional Information:© 2008 American Institute of Physics. Received 15 July 2008; accepted 24 October 2008; published 15 December 2008. This work was supported by grants from the NSF (Grant No. DMS-0349195) and the NIH (Grant No. K25 AI41935). The authors thank J. Genereux, A.K. Boal, and J.K. Barton for helpful discussions.
Funders:
Funding AgencyGrant Number
NSFDMS-0349195
NIHK25 AI41935
Subject Keywords:biotransport, DNA, enzymes, molecular biophysics, Monte Carlo methods, stochastic processes
Issue or Number:23
Record Number:CaltechAUTHORS:FOKjcp08
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:FOKjcp08
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:12632
Collection:CaltechAUTHORS
Deposited By: Archive Administrator
Deposited On:16 Dec 2008 05:39
Last Modified:15 Apr 2017 04:12

Repository Staff Only: item control page