Dose-Dependent Shift in Relative Contribution of Homologous Recombination to DNA Repair after Low-LET Ionizing Radiation Exposure: Empirical Evidence and Numerical Simulation

被引:3
|
作者
Belov, Oleg [1 ,2 ,3 ]
Chigasova, Anna [4 ,5 ]
Pustovalova, Margarita [6 ,7 ]
Osipov, Andrey [4 ]
Eremin, Petr [8 ]
Vorobyeva, Natalia [4 ,6 ]
Osipov, Andreyan N. [1 ,4 ,6 ,7 ]
机构
[1] Joint Inst Nucl Res, 6 Joliot Curie St, Dubna 141980, Russia
[2] Russian Acad Sci, Inst Biomed Problems, 76A Khoroshevskoye Shosse, Moscow 123007, Russia
[3] Dubna State Univ, Inst Syst Anal & Management, 19 Univ Skaya St, Dubna 141980, Russia
[4] Russian Acad Sci, NN Semenov Fed Res Ctr Chem Phys, Moscow 119991, Russia
[5] Russian Acad Sci, Emanuel Inst Biochem Phys, Moscow 119334, Russia
[6] Fed Med Biol Agcy SRC FMBC, State Res Ctr, Burnasyan Fed Med Biophys Ctr, Moscow 123098, Russia
[7] Moscow Inst Phys & Technol, Sch Biol & Med Phys, Dolgoprudnyi 141700, Russia
[8] Minist Hlth Russia, FSBI Natl Med Res Ctr Rehabil & Balneol, Moscow 121099, Russia
基金
俄罗斯科学基金会;
关键词
DNA double-strand breaks; ionizing radiation; DNA repair pathways; homologous recombination; mathematical modeling; DOUBLE-STRAND BREAKS; LINEAR-ENERGY-TRANSFER; MAMMALIAN-CELLS; DSB-REPAIR; ADAPTIVE RESPONSE; GAMMA-H2AX FOCI; DAMAGE; MODEL; KINETICS; STRESS;
D O I
10.3390/cimb45090465
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Understanding the relative contributions of different repair pathways to radiation-induced DNA damage responses remains a challenging issue in terms of studying the radiation injury endpoints. The comparative manifestation of homologous recombination (HR) after irradiation with different doses greatly determines the overall effectiveness of recovery in a dividing cell after irradiation, since HR is an error-free mechanism intended to perform the repair of DNA double-strand breaks (DSB) during S/G2 phases of the cell cycle. In this article, we present experimentally observed evidence of dose-dependent shifts in the relative contributions of HR in human fibroblasts after X-ray exposure at doses in the range 20-1000 mGy, which is also supported by quantitative modeling of DNA DSB repair. Our findings indicate that the increase in the radiation dose leads to a dose-dependent decrease in the relative contribution of HR in the entire repair process.
引用
收藏
页码:7352 / 7373
页数:22
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