TY - JOUR
T1 - P53 deficiency augments nucleolar instability after ionizing irradiation
AU - Kakoti, Sangeeta
AU - Yamauchi, Motohiro
AU - Gu, Wenchao
AU - Kato, Reona
AU - Yasuhara, Takaaki
AU - Hagiwara, Yoshihiko
AU - Laskar, Siddhartha
AU - Oike, Takahiro
AU - Sato, Hiro
AU - Held, Kathryn D.
AU - Nakano, Takashi
AU - Shibata, Atsushi
N1 - Funding Information:
The present study was supported by Grants-in-Aid from the Japan Society for the Promotion of Science for KAKENHI (JP17H04713 to AS), the Takeda Science Foundation, the Uehara Memorial Foundation, and the Program of the network-type Joint Usage/Research Center for Radiation Disaster Medical Science of Hiroshima University, Nagasaki University and Fukushima Medical University. The present study was also supported by Grants-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan for programs for Leading Graduate Schools, Cultivating Global Leaders in Heavy Ion Therapeutics and Engineering.
Publisher Copyright:
© 2019 Spandidos Publications. All rights reserved.
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
KW - Cancer development
KW - Chromosome rearrangement
KW - rDNA gene expression
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U2 - 10.3892/or.2019.7341
DO - 10.3892/or.2019.7341
M3 - Article
C2 - 31578593
AN - SCOPUS:85074499854
SN - 1021-335X
VL - 42
SP - 2293
EP - 2302
JO - Oncology Reports
JF - Oncology Reports
IS - 6
ER -
