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Modeling of DNA Damage Repair and Cell Response in Relation to p53 System Exposed to Ionizing Radiation

Repair of DNA damage induced by ionizing radiation plays an important role in the cell response to ionizing radiation. Radiation-induced DNA damage also activates the p53 system, which determines the fate of cells. The kinetics of repair, which is affected by the cell itself and the complexity of DN...

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Autores principales: Hu, Ankang, Zhou, Wanyi, Wu, Zhen, Zhang, Hui, Li, Junli, Qiu, Rui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9569799/
https://www.ncbi.nlm.nih.gov/pubmed/36232625
http://dx.doi.org/10.3390/ijms231911323
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author Hu, Ankang
Zhou, Wanyi
Wu, Zhen
Zhang, Hui
Li, Junli
Qiu, Rui
author_facet Hu, Ankang
Zhou, Wanyi
Wu, Zhen
Zhang, Hui
Li, Junli
Qiu, Rui
author_sort Hu, Ankang
collection PubMed
description Repair of DNA damage induced by ionizing radiation plays an important role in the cell response to ionizing radiation. Radiation-induced DNA damage also activates the p53 system, which determines the fate of cells. The kinetics of repair, which is affected by the cell itself and the complexity of DNA damage, influences the cell response and fate via affecting the p53 system. To mechanistically study the influences of the cell response to different LET radiations, we introduce a new repair module and a p53 system model with NASIC, a Monte Carlo track structure code. The factors determining the kinetics of the double-strand break (DSB) repair are modeled, including the chromosome environment and complexity of DSB. The kinetics of DSB repair is modeled considering the resection-dependent and resection-independent compartments. The p53 system is modeled by simulating the interactions among genes and proteins. With this model, the cell responses to low- and high-LET irradiation are simulated, respectively. It is found that the kinetics of DSB repair greatly affects the cell fate and later biological effects. A large number of DSBs and a slow repair process lead to severe biological consequences. High-LET radiation induces more complex DSBs, which can be repaired by slow processes, subsequently resulting in a longer cycle arrest and, furthermore, apoptosis and more secreting of TGFβ. The Monte Carlo track structure simulation with a more realistic repair module and the p53 system model developed in this study can expand the functions of the NASIC code in simulating mechanical radiobiological effects.
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spelling pubmed-95697992022-10-17 Modeling of DNA Damage Repair and Cell Response in Relation to p53 System Exposed to Ionizing Radiation Hu, Ankang Zhou, Wanyi Wu, Zhen Zhang, Hui Li, Junli Qiu, Rui Int J Mol Sci Article Repair of DNA damage induced by ionizing radiation plays an important role in the cell response to ionizing radiation. Radiation-induced DNA damage also activates the p53 system, which determines the fate of cells. The kinetics of repair, which is affected by the cell itself and the complexity of DNA damage, influences the cell response and fate via affecting the p53 system. To mechanistically study the influences of the cell response to different LET radiations, we introduce a new repair module and a p53 system model with NASIC, a Monte Carlo track structure code. The factors determining the kinetics of the double-strand break (DSB) repair are modeled, including the chromosome environment and complexity of DSB. The kinetics of DSB repair is modeled considering the resection-dependent and resection-independent compartments. The p53 system is modeled by simulating the interactions among genes and proteins. With this model, the cell responses to low- and high-LET irradiation are simulated, respectively. It is found that the kinetics of DSB repair greatly affects the cell fate and later biological effects. A large number of DSBs and a slow repair process lead to severe biological consequences. High-LET radiation induces more complex DSBs, which can be repaired by slow processes, subsequently resulting in a longer cycle arrest and, furthermore, apoptosis and more secreting of TGFβ. The Monte Carlo track structure simulation with a more realistic repair module and the p53 system model developed in this study can expand the functions of the NASIC code in simulating mechanical radiobiological effects. MDPI 2022-09-26 /pmc/articles/PMC9569799/ /pubmed/36232625 http://dx.doi.org/10.3390/ijms231911323 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hu, Ankang
Zhou, Wanyi
Wu, Zhen
Zhang, Hui
Li, Junli
Qiu, Rui
Modeling of DNA Damage Repair and Cell Response in Relation to p53 System Exposed to Ionizing Radiation
title Modeling of DNA Damage Repair and Cell Response in Relation to p53 System Exposed to Ionizing Radiation
title_full Modeling of DNA Damage Repair and Cell Response in Relation to p53 System Exposed to Ionizing Radiation
title_fullStr Modeling of DNA Damage Repair and Cell Response in Relation to p53 System Exposed to Ionizing Radiation
title_full_unstemmed Modeling of DNA Damage Repair and Cell Response in Relation to p53 System Exposed to Ionizing Radiation
title_short Modeling of DNA Damage Repair and Cell Response in Relation to p53 System Exposed to Ionizing Radiation
title_sort modeling of dna damage repair and cell response in relation to p53 system exposed to ionizing radiation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9569799/
https://www.ncbi.nlm.nih.gov/pubmed/36232625
http://dx.doi.org/10.3390/ijms231911323
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