The DOI matches its Crossref record; 61 of the 61 references it cites were found in a registry or an index.
Cdk2 Is Required for p53-Independent G2/M Checkpoint Control
Open accessAbstract
The activation of phase-specific cyclin-dependent kinases (Cdks) is associated with ordered cell cycle transitions. Among the mammalian Cdks, only Cdk1 is essential for somatic cell proliferation. Cdk1 can apparently substitute for Cdk2, Cdk4, and Cdk6, which are individually dispensable in mice. It is unclear if all functions of non-essential Cdks are fully redundant with Cdk1. Using a genetic approach, we show that Cdk2, the S-phase Cdk, uniquely controls the G(2)/M checkpoint that prevents cells with damaged DNA from initiating mitosis. CDK2-nullizygous human cells exposed to ionizing radiation failed to exclude Cdk1 from the nucleus and exhibited a marked defect in G(2)/M arrest that was unmasked by the disruption of P53. The DNA replication licensing protein Cdc6, which is normally stabilized by Cdk2, was physically associated with the checkpoint regulator ATR and was required for efficient ATR-Chk1-Cdc25A signaling. These findings demonstrate that Cdk2 maintains a balance of S-phase regulatory proteins and thereby coordinates subsequent p53-independent G(2)/M checkpoint activation.
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“Recently, Chung and Bunz have shown that Cdk2 is required for a p53-independent, but Chk1- and Chk2-dependent cell cycle arrest [60]”
From NER initiation factors, DDB2 and XPC, regulate UV radiation response by recruiting ATR and ATM kinases to DNA damage sites (2013) · cites this paper as [60]
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Cites
Cell cycle, CDKs and cancer: a changing paradigm
Malumbres, M., & Barbacid, M. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2602 · Cited by 3,957
Cell-cycle checkpoints and cancer
Kastan, M. B., & Bartek, J. (2004) · Nature · doi:10.1038/nature03097 · Cited by 2,836
Requirement for p53 and p21 to Sustain G 2 Arrest After DNA Damage
Bunz, F., Dutriaux, A., Lengauer, C., Waldman, T., Zhou, S., Brown, J. P., Sedivy, J. M., Kinzler, K. W., & Vogelstein, B. (1998) · Science · doi:10.1126/science.282.5393.1497 · Cited by 2,803
Self-citationAn Oncogene-Induced DNA Damage Model for Cancer Development
Halazonetis, T. D., Gorgoulis, V. G., & Bartek, J. (2008) · Science · doi:10.1126/science.1140735 · Cited by 1,851
ATR: an essential regulator of genome integrity
Cimprich, K. A., & Cortez, D. (2008) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2450 · Cited by 1,798
The DNA Damage Response: Ten Years After
Harper, J. W., & Elledge, S. J. (2007) · Molecular Cell · doi:10.1016/j.molcel.2007.11.015 · Cited by 1,705
Liu, Q., Guntuku, S., Cui, X.-S., Matsuoka, S., Cortez, D., Tamai, K., Luo, G., Carattini-Rivera, S., DeMayo, F., Bradley, A., et al. (2000) · Genes & Development · doi:10.1101/gad.14.12.1448 · Cited by 1,625
Mammalian cyclin-dependent kinases
Malumbres, M., & Barbacid, M. (2005) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2005.09.005 · Cited by 1,333
p21 is necessary for the p53-mediated G1 arrest in human cancer cells.
Waldman, T. A., Kinzler, K. W., & Vogelstein, B. (1995) · PubMed · Cited by 1,188
Cdk1 is sufficient to drive the mammalian cell cycle
Santamarı́a, D., Barrière, C., Cerqueira, A., Hunt, S. L., Tardy, C., Newton, K., Cáceres, J. F., Dubus, P. R., Malumbres, M., & Barbacid, M. (2007) · Nature · doi:10.1038/nature06046 · Cited by 1,096
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Bačević, K. (2016) · theses.fr (ABES) · doi:10.70675/11789f75zbd23z4799zacfbzd7a0d55a3fd3
Oukhdouch, A., Nadir, Y., Salman, E. M., Khalid, J., Zinbi, B., Souad, S., & rais, H. (2026) · Journal of Genetic Engineering and Biotechnology · doi:10.1016/j.jgeb.2026.100724
Aboosi, I. T. S. A., & Fahad, M. M. (2026) · Journal of the Indian Chemical Society · doi:10.1016/j.jics.2026.103053
Wu, Y., Li, Q., Zhu, C., Luo, J., & Zhu, B. (2026) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2026.179352
Metadata
- Authors
- Chung, J. H., & Bunz, F.
- Affiliations
- Johns Hopkins University (US)
- Corresponding author
- Bunz, Fred
- Venue
- PLoS Genetics
- Publisher
- Public Library of Science (PLoS)
- Published
- 2010-02-26
- Volume
- 6
- Issue
- 2
- Pages
- e1000863
- ISSN
- 1553-7390 (ISSN-L)
- 1553-7404
- PMC
- PMC2829054
- OpenAlex
- W2093147524
- Cited by
- 105
- References
- 61
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 5 · 2023: 6 · 2022: 3 · 2021: 6 · 2020: 5 · 2019: 7 · 2018: 5 · 2017: 12 · 2016: 3 · 2015: 1 · 2014: 7 · 2013: 11 · 2012: 10
- FWCI
- 5.07
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS Genetics (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- W. W. Smith Charitable Trust
- Flight Attendant Medical Research Institute
- National Cancer Institute (CA 104253, R01CA104253)
- 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
- CDK2, G2/M checkpoint, CDK1, CDC6, ATR, Chk1, CDC25A, ionizing radiation, DNA damage response, DNA replication licensing
- MeSH terms
- Checkpoint Kinase 1, Animals, Cytoplasm, Enzyme Activation, Enzyme Stability, Humans, Mitosis, Models, Biological, Nuclear Proteins, Phosphorylation, Protein Kinases, Protein Processing, Post-Translational, Radiation, Ionizing, Tumor Suppressor Protein p53, G2 Phase, Protein Serine-Threonine Kinases, Cell Cycle Proteins, cdc25 Phosphatases, Protein Transport, HCT116 Cells, Cyclin-Dependent Kinase 2, Mice, Ataxia Telangiectasia Mutated Proteins
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