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JOURNALS // Computer Research and Modeling // Archive

Computer Research and Modeling, 2015 Volume 7, Issue 1, Pages 159–176 (Mi crm176)

This article is cited in 3 papers

ANALYSIS AND MODELING OF COMPLEX LIVING SYSTEMS

Kinetic model of dna double-strand break repair in primary human fibroblasts exposed to low-let irradiation with various dose rates

I. V. Ozerovab, A. N. Osipovb

a Lomonosov Moscow State University, Faculty of biology, 1-12 Leninskie Gory, Moscow, 119234, Russia
b State Research Center — Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency, 46 Zhivopisnaya st., Moscow, 123182, Russia

Abstract: Here we demonstrate the results of kinetic modeilng of DNA double-strand breaks induction and repair and phosphorilated histone H2AX ($\rm \gamma -H2AX$) and Rad51 foci formation in primary human fibroblasts exposed to low-LET ionizing radiation (IR). The model describes two major paths of DNA double-strand breaks repair: non-homologous end joining (NHEJ) and homologous recombination (HR) and considers interactions between DNA and several repair proteins (DNA-PKcs, ATM, Ku70/80, XRCC1, XRCC4, Rad51, RPA, etc.) using mass action equations and Michaelis-Menten kinetics. Experimental data on DNA rejoining kinetics and $\rm \gamma -H2AX$ and Rad51 foci formation in vicinity of double strand breaks in primary human fibroblasts exposed to low-LET IR with various dose rates and exposure times was utilized for training and statistical validation of the model.

Keywords: DNA double-strand breaks, DNA repair, kinetic modeling, low-LET ionizing radiation, dose rate.

UDC: 577.31

Received: 04.02.2015

DOI: 10.20537/2076-7633-2015-7-1-159-176



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