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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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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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. |
format | Online Article Text |
id | pubmed-9569799 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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