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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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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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