p53 deficiency augments nucleolar instability after ionizing irradiation

Area of Science:

• Molecular Biology
• Cell Biology
• Genetics

Background:

• Ribosomes are crucial for cellular homeostasis via protein synthesis.
• The nucleolus houses ribosomal DNA (rDNA) encoding ribosomal RNA (rRNA), essential for ribosome biogenesis.
• The DNA damage response's effect on rDNA stability and nucleolar integrity remains understudied.

Purpose of the Study:

• To investigate the impact of DNA damage on nucleolar stability.
• To examine changes in nucleolin, a nucleolar marker, following ionizing radiation (IR).
• To elucidate the role of p53 in nucleolar response to DNA damage.

Main Methods:

• Exposure of HCT116 and U2OS cells to ionizing radiation (IR).
• Microscopic analysis of nucleolin number and morphology to assess nucleolar changes.
• Assessment of ribosomal RNA (rRNA) synthesis in response to IR and p53 status.

Main Results:

• IR increased nucleoli number per cell in both cell lines.
• IR-induced nucleolar fragmentation was exacerbated by p53 deficiency.
• p53 deficiency led to decreased rRNA synthesis following IR, indicating impaired rDNA transcription.

Conclusions:

• p53 plays a critical role in maintaining nucleolar stability and rDNA transcriptional activity following DNA damage.
• Nucleolar fragmentation correlates with reduced rRNA synthesis, impacting cellular homeostasis.
• The study reveals distinct patterns of nucleolar morphology changes dependent on cell type and p53 status.