Use of the Comet-FISH Assay to Compare DNA Damage and Repair in p53 and hTERT Genes following Ionizing Radiation

Ionizing radiation (IR) is considered a traditional mutagen and genotoxic agent. Exposure to IR affects in all cases biological systems and living organisms from plants to humans mostly in a pernicious way. At low (<0.1 Gy) and low-to-medium doses (0.1–1 Gy), one can find in the literature a variety of findings indicating sometimes a positive-like anti-inflammatory effect or detrimental-like toxicity. In this Special Issue and in general in the current research, we would like to acquire works and more knowledge on the role(s) of DNA damage and its repair induced by ionizing radiations as instigators of the full range of biological responses to radiation. Emphasis should be given to advances offering mechanistic insights into the ability of radiations with different qualities to severely impact cells or tissues. High-quality research or review studies on different species projected to humans are welcome. Technical advances reporting on the methodologies to accurately measure DNA or other types of biological damage must be highly considered for the near future in our research community, as well. Last but not least, clinical trials or protocols with improvements to radiation therapy and radiation protection are also included in our vision for the advancement of research regarding biological effects of IR.

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Silencing of E3 Ubiquitin Ligase RNF8 Enhances Ionizing Radiation Sensitivity of Medulloblastoma Cells by Promoting the Deubiquitination of PCNA

Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics ◽

10.3727/096504018x15154085345907 ◽

2018 ◽

Vol 26 (9) ◽

pp. 1365-1373

Author(s):

Fei Li ◽

Bin Liu ◽

Xiaolan Zhou ◽

Quan Xu

Keyword(s):

Dna Damage ◽

Ionizing Radiation ◽

Dna Damage Response ◽

Ubiquitin Ligase ◽

Dna Damage Repair ◽

E3 Ubiquitin Ligase ◽

Dna Damage And Repair ◽

Damage Repair ◽

Damage Response ◽

Γ Ray

DNA damage response induced by ionizing radiation (IR) is an important event involved in the sensitivity and efficiency of radiotherapy in human medulloblastoma. RNF8 is an E3 ubiquitin ligase and has key roles in the process of DNA damage and repair. Our study aimed to evaluate the effect of RNF8 in the DNA damage repair induced by IR exposure in medulloblastoma cells. We found that the levels of RNF8 were significantly upregulated by γ-ray irradiation in a dose-dependent manner in medulloblastoma cells and colocalized with γ-H2AX, a sensitive marker of DNA double-strand breaks induced by γ-ray radiation. RNF8 knockdown was observed to enhance the sensitivity of IR in medulloblastoma cells, as evaluated by reduced cell survival. The apoptosis and cell cycle arrest of medulloblastoma cells were dramatically increased by RNF8 suppression after IR treatment. Furthermore, RNF8 inhibition did not affect the protein levels of BRCA1, a crucial protein involved in IR-induced DNA damage repair, but significantly decreased the recruitment of BRCA1 and increased the level of γ-H2AX at DNA damage sites compared to the control. A significant increase in OTM was observed in medulloblastoma cells treated by RNF8 shRNA after exposure to IR, indicating the effect of RNF8 on DNA damage and repair. Additionally, PCNA, a major target for ubiquitin modification during DNA damage response, was found to be monoubiquitinated by E3 ligase RNF8 and might contribute to the low radiosensitivity in medulloblastoma cells. Altogether, our findings may provide RNF8 as a novel target for the improvement of radiotherapy in medulloblastoma.

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Analysis of ionizing radiation-induced DNA damage and repair in three-dimensional human skin model system

Experimental Dermatology ◽

10.1111/j.1600-0625.2009.00945.x ◽

2009 ◽

Vol 19 (8) ◽

pp. e16-e22 ◽

Cited By ~ 22

Author(s):

Yanrong Su ◽

Jarah A. Meador ◽

Charles R. Geard ◽

Adayabalam S. Balajee

Keyword(s):

Dna Damage ◽

Ionizing Radiation ◽

Human Skin ◽

Three Dimensional ◽

Model System ◽

Skin Model ◽

Dna Damage And Repair ◽

Radiation Induced

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Relative Contributions of Levels of Initial DNA Damage and Repair of Double Strand Breaks to the Ionizing Radiation-sensitive Phenotype of the Chinese Hamster Cell Mutant, XR-V15B. Part I. X-rays

International Journal of Radiation Biology ◽

10.1080/09553009314450791 ◽

1993 ◽

Vol 63 (5) ◽

pp. 609-616 ◽

Cited By ~ 29

Author(s):

B.P. Kysela ◽

B.D. Michael ◽

J.E. Arrand

Keyword(s):

Dna Damage ◽

Ionizing Radiation ◽

Chinese Hamster ◽

Chinese Hamster Cell ◽

Double Strand Breaks ◽

X Rays ◽

Cell Mutant ◽

Dna Damage And Repair ◽

Strand Breaks

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Mutational impact and signature of ionizing radiation

10.1101/2021.01.12.426324 ◽

2021 ◽

Author(s):

Jeonghwan Youk ◽

Hyun Woo Kwon ◽

Joonoh Lim ◽

Eunji Kim ◽

Ryul Kim ◽

...

Keyword(s):

Dna Damage ◽

Ionizing Radiation ◽

Mammalian Cells ◽

Single Cells ◽

Dna Double Strand Breaks ◽

Structural Variations ◽

Dna Damage And Repair ◽

Repair Processes ◽

Massive Number ◽

Chaotic Nature

AbstractWhole-genome sequencing (WGS) of human tumors and normal cells exposed to various carcinogens has revealed distinct mutational patterns that provide deep insights into the DNA damage and repair processes. Although ionizing radiation (IR) is conventionally known as a strong carcinogen, its genome-wide mutational impacts have not been comprehensively investigated at the single-nucleotide level. Here, we explored the mutational landscape of normal single-cells after exposure to the various levels of IR. On average, 1 Gy of IR exposure generated ∼16 mutational events with a spectrum consisting of predominantly small nucleotide deletions and a few characteristic structural variations. In ∼30% of the post-irradiated cells, complex genomic rearrangements, such as chromoplexy, chromothripsis, and breakage-fusion-bridge cycles, were resulted, indicating the stochastic and chaotic nature of DNA repair in the presence of the massive number of concurrent DNA double-strand breaks. These mutational signatures were confirmed in the genomes of 22 IR-induced secondary malignancies. With high-resolution genomic snapshots of irradiated cells, our findings provide deep insights into how IR-induced DNA damage and subsequent repair processes operate in mammalian cells.

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