Journal article
A quantitative model of human DNA base excision repair. I. Mechanistic insights
Nucleic acids research, v 30(8), pp 1817-1825
15 Apr 2002
PMID: 11937636
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Base excision repair (BER) is a multistep process involving the sequential activity of several proteins that cope with spontaneous and environmentally induced mutagenic and cytotoxic DNA damage. Quantitative kinetic data on single proteins of BER have been used here to develop a mathematical model of the BER pathway. This model was then employed to evaluate mechanistic issues and to determine the sensitivity of pathway throughput to altered enzyme kinetics. Notably, the model predicts considerably less pathway throughput than observed in experimental in vitro assays. This finding, in combination with the effects of pathway cooperativity on model throughput, supports the hypothesis of cooperation during abasic site repair and between the apurinic/apyrimidinic (AP) endonuclease, Ape1, and the 8-oxoguanine DNA glycosylase, Ogg1. The quantitative model also predicts that for 8-oxoguanine and hydrolytic AP site damage, short-patch Polbeta-mediated BER dominates, with minimal switching to the long-patch subpathway. Sensitivity analysis of the model indicates that the Polbeta-catalyzed reactions have the most control over pathway throughput, although other BER reactions contribute to pathway efficiency as well. The studies within represent a first step in a developing effort to create a predictive model for BER cellular capacity.
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Details
- Title
- A quantitative model of human DNA base excision repair. I. Mechanistic insights
- Creators
- Bahrad A Sokhansanj - Lawrence Livermore National LaboratoryGarry R RodrigueJ Patrick FitchDavid M Wilson
- Publication Details
- Nucleic acids research, v 30(8), pp 1817-1825
- Publisher
- Oxford University Press
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Electrical and Computer Engineering
- Web of Science ID
- WOS:000174797300015
- Scopus ID
- 2-s2.0-0037089147
- Other Identifier
- 991019186962604721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology