p53 deficiency augments nucleolar instability after ionizing irradiation

Kakoti,Sangeeta; Yamauchi,Motohiro; Gu,Wenchao; Kato,Reona; Yasuhara,Takaaki; Hagiwara,Yoshihiko; Laskar,Siddhartha; Oike,Takahiro; Sato,Hiro; Held,Kathryn   D.; Nakano,Takashi; Shibata,Atsushi

doi:10.3892/or.2019.7341

p53 deficiency augments nucleolar instability after ionizing irradiation

Authors:
- Sangeeta Kakoti
- Motohiro Yamauchi
- Wenchao Gu
- Reona Kato
- Takaaki Yasuhara
- Yoshihiko Hagiwara
- Siddhartha Laskar
- Takahiro Oike
- Hiro Sato
- Kathryn D. Held
- Takashi Nakano
- Atsushi Shibata
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Affiliations: Gunma University Initiative for Advanced Research (GIAR), Maebashi, Gunma 371‑8511, Japan, Department of Radiation Biology and Protection, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki 852‑8523, Japan, Laboratory of Molecular Radiology, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo 113‑8655, Japan, Department of Radiation Oncology, Gunma University Graduate School of Medicine, Maebashi, Gunma 371‑8511, Japan, Department of Radiation Oncology, Tata Memorial Hospital, Mumbai 400012, India, Department of Radiation Oncology, Massachusetts General Hospital/Harvard Medical School, Boston, MA 02114, USA
Published online on: September 27, 2019 https://doi.org/10.3892/or.2019.7341
Pages: 2293-2302
Copyright: © Kakoti et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Ribosomes are important cellular components that maintain cellular homeostasis through overall protein synthesis. The nucleolus is a prominent subnuclear structure that contains ribosomal DNA (rDNA) encoding ribosomal RNA (rRNA), an essential component of ribosomes. Despite the significant role of the rDNA‑rRNA‑ribosome axis in cellular homeostasis, the stability of rDNA in the context of the DNA damage response has not been fully investigated. In the present study, the number and morphological changes of nucleolin, a marker of the nucleolus, were examined following ionizing radiation (IR) in order to investigate the impact of DNA damage on nucleolar stability. An increase in the number of nucleoli per cell was found in HCT116 and U2OS cells following IR. Interestingly, the IR‑dependent increase in nucleolar fragmentation was enhanced by p53 deficiency. In addition, the morphological analysis revealed several distinct types of nucleolar fragmentation following IR. The pattern of nucleolar morphology differed between HCT116 and U2OS cells, and the p53 deficiency altered the pattern of nucleolar morphology. Finally, a significant decrease in rRNA synthesis was observed in HCT116 p53‑/‑ cells following IR, suggesting that severe nucleolar fragmentation downregulates rRNA transcription. The findings of the present study suggest that p53 plays a key role in protecting the transcriptional activity of rDNA in response to DNA damage.

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