Charge transport-mediated recruitment of DNA repair enzymes

التفاصيل البيبلوغرافية
العنوان: Charge transport-mediated recruitment of DNA repair enzymes
المؤلفون: Fok, Pak-Wing, Guo, Chin-Lin, Chou, Tom
المصدر: Journal of Chemical Physics, 129, 235101, (2008)
سنة النشر: 2008
المجموعة: Quantitative Biology
مصطلحات موضوعية: Quantitative Biology - Biomolecules, Quantitative Biology - Subcellular Processes
الوصف: Damaged or mismatched bases in DNA can be repaired by Base Excision Repair (BER) enzymes 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, {\it et al.}, PNAS, {\bf 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.
Comment: 9 Figures, Accepted to J. Chem. Phys
نوع الوثيقة: Working Paper
DOI: 10.1063/1.3026735
الوصول الحر: http://arxiv.org/abs/0811.2837Test
رقم الانضمام: edsarx.0811.2837
قاعدة البيانات: arXiv