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Requirement for p53 and p21 to Sustain G 2 Arrest After DNA Damage
Abstract
After DNA damage, many cells appear to enter a sustained arrest in the G 2 phase of the cell cycle. It is shown here that this arrest could be sustained only when p53 was present in the cell and capable of transcriptionally activating the cyclin-dependent kinase inhibitor p21. After disruption of either the p53 or the p21 gene, γ radiated cells progressed into mitosis and exhibited a G 2 DNA content only because of a failure of cytokinesis. Thus, p53 and p21 appear to be essential for maintaining the G 2 checkpoint in human cells.
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“p21 is required for p53-mediated G1/S146, 147, 148 and also for G2/M cell cycle arrest.149”
From Census and evaluation of p53 target genes (2017) · cites this paper as [149]
In the citing paper
“Indeed, after transiently arresting in G2, HCT-116 cells in which p21 was knocked out eventually underwent aberrant mitoses, leading to polyploidy or cell death.53,55”
From Senescence from G2 arrest, revisited (2015) · cites this paper as [55]
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Metadata
- Authors
- Bunz, F., Dutriaux, A., Lengauer, C., Waldman, T., Zhou, S., Brown, J. P., Sedivy, J. M., Kinzler, K. W., & Vogelstein, B.
- Affiliations
- Howard Hughes Medical Institute (US)
- F. Bunz, S. Zhou, B. Vogelstein, The Howard Hughes Medical Institute and The Johns Hopkins Oncology Center, 424 North Bond Street, Baltimore, MD 21231, USA. C. Lengauer and K. W. Kinzler, The Johns Hopkins Oncology Center, Baltimore, MD 21231, USA. A. Dutriaux, J. P. Brown, J. Sedivy, Department of Molecular Biology, Cell Biology, and Biochemistry, Division of Biology and Medicine, Brown University, Providence, RI 02912, USA. T. Waldman, Program in Human Genetics and the Johns Hopkins Oncology...
- Corresponding author
- Vogelstein, B.
- Venue
- Science
- Published
- 1998-11-20
- Volume
- 282
- Issue
- 5393
- Pages
- 1497-1501
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2080125477
- Cited by
- 2,803
- References
- 50
- Citations by year
- 2026: 28 · 2025: 39 · 2024: 42 · 2023: 60 · 2022: 69 · 2021: 86 · 2020: 77 · 2019: 76 · 2018: 98 · 2017: 101 · 2016: 103 · 2015: 97 · 2014: 113 · 2013: 155 · 2012: 120
- FWCI
- 41.60
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (CA 57345, CA43460, P50CA062924, CA 62924)
- 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 › Cell Biology › Microtubule and mitosis dynamics
- Keywords
- p53, p21, G2 checkpoint, DNA damage, cell cycle arrest, cyclin-dependent kinase inhibitors, transcriptional activation, gamma radiation, cytokinesis, mitosis, gene disruption
- MeSH terms
- Cell Line, DNA, DNA Damage, Gamma Rays, Gene Expression Regulation, Humans, Mitosis, Mutation, Tumor Cells, Cultured, Nocodazole, Genes, p53, Tumor Suppressor Protein p53, G2 Phase, CDC2 Protein Kinase, Cyclins, Apoptosis, Cyclin B, Cyclin-Dependent Kinase Inhibitor p21, Cyclin B1
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