Cited by 904Cancer-related Molecular PathwaysDNA Repair MechanismsBiochemical and Molecular Research

A ribonucleotide reductase gene involved in a p53-dependent cell-cycle checkpoint for DNA damage

Tanaka, Hiroshi, Arakawa, Hirofumi, Yamaguchi, Tatsuya, Shiraishi, Kenji, Fukuda, Seisuke, Matsui, Kuniko, Takei, Yoshiki, Nakamura, Yusuke·2000·Nature

Abstract

The p53 gene is frequently inactivated in human cancers. Here we have isolated a p53-inducible gene, p53R2, by using differential display to examine messenger RNAs in a cancer-derived human cell line carrying a highly regulated wild-type p53 expression system. p53R2 contains a p53-binding sequence in intron 1 and encodes a 351-amino-acid peptide with striking similarity to the ribonucleotide reductase small subunit (R2), which is important in DNA synthesis during cell division. Expression of p53R2, but not R2, was induced by ultraviolet and gamma-irradiation and adriamycin treatment in a wild-type p53-dependent manner. Induction of p53R2 in p53-deficient cells caused G2/M arrest and prevented cells from death in response to adriamycin. Inhibition of endogenous p53R2 expression in cells that have an intact p53-dependent DNA damage checkpoint reduced ribonucleotide reductase activity, DNA repair and cell survival after exposure to various genotoxins. Our results indicate that p53R2 encodes a ribonucleotide reductase that is directly involved in the p53 checkpoint for repair of damaged DNA. The discovery of p53R2 clarifies a relationship between a ribonucleotide reductase activity involved in repair of damaged DNA and tumour suppression by p53.

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Crossref · 10.1038/35003506

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  • RRM2B encodes a ribonucleotide reductase that fuels DNA repair by supplying precursors, and is targeted by p53.

    “RRM2B encodes for a ribonucleotide reductase that fuels DNA repair by supplying precursors, and is targeted by p53.31”

    From Census and evaluation of p53 target genes (2017) · cites this paper as [31]

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Authors
Tanaka, H., Arakawa, H., Yamaguchi, T., Shiraishi, K., Fukuda, S., Matsui, K., Takei, Y., & Nakamura, Y.
Affiliations
Institute of Medical Science, The University of Tokyo (JP)
Corresponding author
Nakamura, Yusuke
Venue
Nature
Published
2000-03
Volume
404
Issue
6773
Pages
42-49
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
OpenAlex
W1680634601
Cited by
904
References
42
Citations by year
2026: 12 · 2025: 16 · 2024: 12 · 2023: 19 · 2022: 16 · 2021: 22 · 2020: 15 · 2019: 24 · 2018: 28 · 2017: 29 · 2016: 38 · 2015: 41 · 2014: 43 · 2013: 36 · 2012: 47
FWCI
27.23
Type
journal article
Language
en
Open access
closed
Locations
  • Nature (publishedVersion)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
Topics
  • Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Molecular Research
Keywords
p53R2, ribonucleotide reductase, p53, DNA damage checkpoint, G2/M cell cycle arrest, DNA repair, UV irradiation, gamma irradiation, doxorubicin, tumor suppression, genotoxins, p53-deficient cells
MeSH terms
Amino Acid Sequence, Cell Cycle, DNA Damage, DNA Repair, Enzyme Induction, Humans, Molecular Sequence Data, Mutagens, Ribonucleotide Reductases, Transfection, Tumor Cells, Cultured, Gene Expression Regulation, Enzymologic, Tumor Suppressor Protein p53, Sequence Homology, Amino Acid, Cell Cycle Proteins

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