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Updated: Jul 9, 2026
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Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay
Published on: May 3, 2018
Cdc7 kinase mediates Claspin phosphorylation in DNA replication checkpoint
1Genome Dynamics Project, The Tokyo Metropolitan Institute of Medical Science, Bunkyo-ku, Tokyo, Japan.
Oncogene
|December 18, 2007
Summary
Cdc7 kinase is essential for DNA replication checkpoint activation. This study reveals Cdc7 regulates Claspin, a key protein, enabling the ATR-Chk1 pathway to respond to DNA damage.
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- Cdc7 kinase is crucial for DNA replication initiation and progression.
- The specific role of Cdc7 in DNA damage checkpoint responses is not well understood.
Purpose of the Study:
- To investigate the function of Cdc7 kinase in DNA replication checkpoint activation.
- To elucidate the mechanism by which Cdc7 influences checkpoint signaling.
Main Methods:
- Gene deletion in mouse embryonic stem (ES) cells.
- siRNA-mediated depletion of Cdc7 in human cancer cell lines.
- Hydroxyurea (HU) and UV treatment to induce DNA replication stress.
- Analysis of Chk1 activation, ATR and Rad17 chromatin recruitment, and Claspin phosphorylation and association.
Main Results:
- Cdc7 deletion or depletion abrogated hydroxyurea (HU)- or UV-induced Chk1 activation.
- Cdc7-depleted cells showed increased sensitivity to HU treatment.
- ATR and Rad17 correctly localized to chromatin, indicating normal detection of stalled replication forks.
- Cdc7 depletion impaired Claspin chromatin association and phosphorylation.
- Cdc7 was found to interact with and phosphorylate Claspin.
Conclusions:
- Cdc7 kinase is required for the activation of the ATR-Chk1 DNA damage checkpoint pathway.
- Cdc7 regulates Claspin, mediating its role in checkpoint activation.
- Cdc7 plays a critical role in cellular responses to DNA replication stress.
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