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Updated: Jul 9, 2026
10:24
Two- and Three-Dimensional Live Cell Imaging of DNA Damage Response Proteins
Published on: September 28, 2012
p53R2-dependent pathway for DNA synthesis in a p53-regulated cell cycle checkpoint
T Yamaguchi1, K Matsuda, Y Sagiya
1Laboratory of Molecular Medicine and Genome Technology, Human Genome Center, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Cancer Research
|November 24, 2001
Summary
The p53R2 enzyme supplies nucleotides for DNA repair, crucial for cell survival. Its dysfunction can trigger apoptosis, eliminating damaged cells.
Area of Science:
- Molecular Biology
- Cell Biology
- Cancer Research
Background:
- Ribonucleotide reductase (RR) is vital for DNA synthesis.
- p53R2, a p53-regulated RR, supplies nucleotides for DNA repair.
- The role of p53R2 in DNA synthesis and cell cycle checkpoints requires further elucidation.
Purpose of the Study:
- To investigate the function of the p53R2-dependent DNA synthesis pathway.
- To compare p53R2-dependent DNA synthesis with R2-dependent DNA synthesis.
- To explore the implications of p53R2 dysfunction in cancer cells.
Main Methods:
- Gamma-irradiation to induce DNA damage.
- Quantitative analysis of p53R2 and R2 expression levels.
- Cellular localization studies of p53R2 and R2.
- Analysis of p53R2 mutation in HCT116 cancer cells.
- Assessment of apoptosis and p53AIP1 transcriptional activation.
Main Results:
- p53R2 expression, not R2, correlated with increased DNA synthesis post-irradiation.
- p53R2 accumulated in the nucleus, while R2 decreased in the cytoplasm.
- A p53R2 mutation in HCT116 cells led to loss of RR activity.
- Dysfunctional p53R2 enhanced DNA damage-inducible apoptosis via p53AIP1.
Conclusions:
- p53R2-dependent DNA synthesis is critical for nuclear DNA repair and cell survival.
- Impaired p53R2 function may activate p53-dependent apoptosis to eliminate compromised cells.
- This pathway represents a potential target for cancer therapy.
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