Purpose: Track structure Monte Carlo (MC) codes have achieved successful outcomes in the quantitative investigation of radiation-induced initial DNA damage. The aim of the present study is to extend a Geant4-DNA radiobiological application by incorporating a feature allowing for the prediction of DNA rejoining kinetics and corresponding cell surviving fraction along time after irradiation, for a Chinese hamster V79 cell line, which is one of the most popular and widely investigated cell lines in radiobiology.
Methods: We implemented the Two-Lesion Kinetics (TLK) model, originally proposed by Stewart, which allows for simulations to calculate residual DNA damage and surviving fraction along time via the number of initial DNA damage and its complexity as inputs.
Results: By optimizing the model parameters of the TLK model in accordance to the experimental data on V79, we were able to predict both DNA rejoining kinetics at low linear energy transfers (LET) and cell surviving fraction.
Conclusion: This is the first study to demonstrate the implementation of both the cell surviving fraction and the DNA rejoining kinetics with the estimated initial DNA damage, in a realistic cell geometrical model simulated by full track structure MC simulations at DNA level and for various LET. These simulation and model make the link between mechanistic physical/chemical damage processes and these two specific biological endpoints.
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http://dx.doi.org/10.1016/j.ejmp.2022.11.012 | DOI Listing |
Nat Commun
November 2024
School of Molecular Biosciences, University of Glasgow, Bower Building, University Avenue, Glasgow, UK.
Curr Opin Microbiol
December 2024
Department of Microbiology, University of Washington School of Medicine, Seattle, WA 98109, USA. Electronic address:
Topoisomerases are essential, ubiquitous enzymes that break and rejoin the DNA strand to control supercoiling. Because topoisomerases are DNA scissors, these enzymes are highly regulated to avoid excessive DNA cleavage, a vulnerability exploited by many antibiotics. Topoisomerase activity must be co-ordinated in time and space with transcription, replication, and cell division or else these processes stall, leading to genome loss.
View Article and Find Full Text PDFPlant J
October 2024
Kansai Institute for Photon Science, National Institutes for Quantum Science and Technology (QST), Kizugawa, 619-0215, Japan.
DNA rearrangements, including inversions, translocations, and large insertions/deletions (indels), are crucial for crop evolution, domestication, and improvement. The rearrangements are frequently induced by ion beams via the mis-repair of DNA double-strand breaks (DSBs). Unfortunately, how ion beam-induced DSBs are repaired has not been comprehensively analyzed and the mechanisms underlying DNA rearrangements remain unclear.
View Article and Find Full Text PDFJ Radiat Res
September 2024
Department of Radiation Oncology, Mayo Clinic, 4450 San Pablo Rd S, Jacksonville, FL 32224, USA.
The repair of DNA double-strand breaks is a crucial yet delicate process which is affected by a multitude of factors. In this study, our goal is to analyse the influence of the linear energy transfer (LET) on the DNA repair kinetics. By utilizing the database of repair of DNA and aggregating the results of 84 experiments, we conduct various model fits to evaluate and compare different hypothesis regarding the effect of LET on the rejoining of DNA ends.
View Article and Find Full Text PDFPeerJ
September 2024
College of Life Science and Technology, Huazhong Agricultural University, Wuhan, China.
Meiosis is a critical process in sexual reproduction, and errors during this cell division can significantly impact fertility. Successful meiosis relies on the coordinated action of numerous genes involved in DNA replication, strand breaks, and subsequent rejoining. DNA topoisomerase enzymes play a vital role by regulating DNA topology, alleviating tension during replication and transcription.
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