Drug Discovery Targeting Post-Translational Modifications in Response to DNA Damages Induced by Space Radiation
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Published:2023-04-21
Issue:8
Volume:24
Page:7656
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ISSN:1422-0067
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Container-title:International Journal of Molecular Sciences
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language:en
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Short-container-title:IJMS
Author:
Xie Dafei1ORCID, Huang Qi12, Zhou Pingkun12ORCID
Affiliation:
1. Department of Radiation Biology, Beijing Key Laboratory for Radiobiology (BKLRB), Beijing Institute of Radiation Medicine, Taiping Road 27th, Haidian District, Beijing 100850, China 2. Department of Preventive Medicine, School of Public Health, University of South China, Changsheng West Road 28th, Zhengxiang District, Hengyang 421001, China
Abstract
DNA damage in astronauts induced by cosmic radiation poses a major barrier to human space exploration. Cellular responses and repair of the most lethal DNA double-strand breaks (DSBs) are crucial for genomic integrity and cell survival. Post-translational modifications (PTMs), including phosphorylation, ubiquitylation, and SUMOylation, are among the regulatory factors modulating a delicate balance and choice between predominant DSB repair pathways, such as non-homologous end joining (NHEJ) and homologous recombination (HR). In this review, we focused on the engagement of proteins in the DNA damage response (DDR) modulated by phosphorylation and ubiquitylation, including ATM, DNA-PKcs, CtIP, MDM2, and ubiquitin ligases. The involvement and function of acetylation, methylation, PARylation, and their essential proteins were also investigated, providing a repository of candidate targets for DDR regulators. However, there is a lack of radioprotectors in spite of their consideration in the discovery of radiosensitizers. We proposed new perspectives for the research and development of future agents against space radiation by the systematic integration and utilization of evolutionary strategies, including multi-omics analyses, rational computing methods, drug repositioning, and combinations of drugs and targets, which may facilitate the use of radioprotectors in practical applications in human space exploration to combat fatal radiation hazards.
Funder
Beijing Natural Science Foundation Young Elite Program National Natural Science Foundation of China
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
Reference241 articles.
1. Ramos, R.L., Carante, M.P., Ferrari, A., Sala, P., Vercesi, V., and Ballarini, F. (2023). A Mission to Mars: Prediction of GCR Doses and Comparison with Astronaut Dose Limits. Int. J. Mol. Sci., 24. 2. Drago-Ferrante, R., Di Fiore, R., Karouia, F., Subbannayya, Y., Das, S., Aydogan Mathyk, B., Arif, S., Guevara-Cerdán, A.P., Seylani, A., and Galsinh, A.S. (2022). Extraterrestrial Gynecology: Could Spaceflight Increase the Risk of Developing Cancer in Female Astronauts? An Updated Review. Int. J. Mol. Sci., 23. 3. Schroeder, M.K., Liu, B., Hinshaw, R.G., Park, M.-A., Wang, S., Dubey, S., Liu, G.G., Shi, Q., Holton, P., and Reiser, V. (2021). Long-Term Sex- and Genotype-Specific Effects of 56Fe Irradiation on Wild-Type and APPswe/PS1dE9 Transgenic Mice. Int. J. Mol. Sci., 22. 4. Cataractogenesis following high-LET radiation exposure;Hamada;Mutat. Res.,2016 5. Rudobeck, E., Bellone, J.A., Szücs, A., Bonnick, K., Mehrotra-Carter, S., Badaut, J., Nelson, G.A., Hartman, R.E., and Vlkolinský, R. (2017). Low-dose proton radiation effects in a transgenic mouse model of Alzheimer’s disease—Implications for space travel. PLoS ONE, 12.
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