Integrating chromosome conformation and DNA repair in a computational framework to assess cell radiosensitivity .

Autor:	Andriotty M; Oak Ridge National Laboratory, Oak Ridge, TN, United States of America.; Georgia Institute of Technology, Atlanta, GA, United States of America., Wang CC; Georgia Institute of Technology, Atlanta, GA, United States of America., Kapadia A; Oak Ridge National Laboratory, Oak Ridge, TN, United States of America., McCord RP; University of Tennessee, Knoxville, Knoxville, TN, United States of America., Agasthya G; Oak Ridge National Laboratory, Oak Ridge, TN, United States of America.
Jazyk:	angličtina
Zdroj:	Physics in medicine and biology [Phys Med Biol] 2024 Dec 13; Vol. 69 (24). Date of Electronic Publication: 2024 Dec 13.
DOI:	10.1088/1361-6560/ad94c6
Abstrakt:	Objective. The arrangement of chromosomes in the cell nucleus has implications for cell radiosensitivity. The development of new tools to utilize Hi-C chromosome conformation data in nanoscale radiation track structure simulations allows for in silico investigation of this phenomenon. We have developed a framework employing Hi-C-based cell nucleus models in Monte Carlo radiation simulations, in conjunction with mechanistic models of DNA repair, to predict not only the initial radiation-induced DNA damage, but also the repair outcomes resulting from this damage, allowing us to investigate the role chromosome conformation plays in the biological outcome of radiation exposure. Approach. In this study, we used this framework to generate cell nucleus models based on Hi-C data from fibroblast and lymphoblastoid cells and explore the effects of cell type-specific chromosome structure on radiation response. The models were used to simulate external beam irradiation including DNA damage and subsequent DNA repair. The kinetics of the simulated DNA repair were compared with previous results. Main results. We found that the fibroblast models resulted in a higher rate of inter-chromosome misrepair than the lymphoblastoid model, despite having similar amounts of initial DNA damage and total misrepairs for each irradiation scenario. Significance. This framework represents a step forward in radiobiological modeling and simulation allowing for more realistic investigation of radiosensitivity in different types of cells. (Creative Commons Attribution license.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu