Russian Journal of Biological Physics and Chemisrty Russian Journal of Biological Physics and Chemisrty АКТУАЛЬНЫЕ ВОПРОСЫ БИОЛОГИЧЕСКОЙ ФИЗИКИ И ХИМИИ 2499-9962 55166 10.29039/rusjbpc.2022.0560 Моделирование в биофизике Modelling in biophycis Моделирование в биофизике MODELING OF DNA DAMAGE REPAIR INDUCED BY HEAVY IONS IN MAMMALIAN CELLS МОДЕЛИРОВАНИЕ РЕПАРАЦИИ ПОВРЕЖДЕНИЙ ДНК, ИНДУЦИРОВАННЫХ ТЯЖЕЛЫМИ ИОНАМИ В КЛЕТКАХ МЛЕКОПИТАЮЩИХ Васильева М. А. Vasil'eva M. A. mal2008@jinr.ru Бугай А. Н. Bugay A. N. Душанов Э. Б Dushanov E. B. Объединенный институт ядерных исследований Дубна Россия Joint Institute for Nuclear Research Dubna Russian Federation Объединенный институт ядерных исследований Дубна Россия Joint Institute for Nuclear Research Dubna Russian Federation Объединенный институт ядерных исследований Дубна Россия Joint Institute for Nuclear Research Dubna Russian Federation 24 11 2022 24 11 2022 7 4 557 564 25 07 2022 https://rusjbpc.ru/en/nauka/article/55166/view

В настоящей работе предложено математическое описание основных путей репарации однонитевых разрывов (ОР) ДНК, повреждений оснований (ПО), двунитевых разрывов (ДР) ДНК в клетках млекопитающих и человека. Модельный подход отражает ключевые молекулярные механизмы восстановления ДНК путем репарации однонитевых разрывов ДНК, эксцизионной репарации оснований (BER), негомологичного воссоединения концов (NHEJ). Для формализации молекулярных механизмов составлена динамическая система из дифференциальных уравнений, описывающая химическую кинетику белковых взаимодействий в соответствии с современными представлениями молекулярной биологии. Учет всех трех репарационных механизмов позволяет более полно описать ответ клетки на облучение тяжелыми заряженными частицами. Предложенная модель корректно описывает основные процессы, протекающие в ходе репарации ОР, BER и NHEJ. В ходе работы рассчитана временная динамика формирования и репарации ключевых типов повреждений ДНК (ПО, ОР, ДР) в клетках человека при действии ионов 56Fe (E = 600 Мэв/нукл). Проведен сравнительный анализ выхода и репарации повреждений ДНК при действии ионов 12C (E = 270 Мэв/нукл) и 56Fe (E = 600 Мэв/нукл) в дозе 1 Гр.

In this paper the mathematical description of main DNA repair pathways of single-strand break (SSB), base damage (BD), and double-strand break (DSB) in mammalian and human cells are proposed. The model shows key molecular mechanisms of DNA recovery through the single-strand DNA repair, base excision repair (BER), nonhomologous end-joining (NHEJ). To formalize the molecular mechanisms the dynamic system of differential equations describing the chemical kinetics of protein interactions according the modern concepts of molecular biology is constructed. Taking into account three repair pathways it makes possible to describe the cell's response to heavy charged particles influence. The proposed model is validated for main mechanisms of SSB repair, BER, NHEJ. In the course of the work, the time-dependent dynamics of formations and repairs of key DNA damage types (BD, SSB, DSB, cluster damages) in human cells under 56Fe ions (E = 600 Mev/u) exposure are calculated. A comparative analysis of the DNA damages and theirs repair under 12C (E = 270 MeV/u) and 56Fe (E = 600 Mev/u) ions exposure at 1 Gy was carried out.

 однонитевые разрывы ДНК двунитевые разрывы ДНК повреждения оснований кластерные разрывы ДНК ЛПЭ репарация моделирование single-strand breaks double-strand breaks base damages LET repair modeling

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