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Updated: May 7, 2026
10:24
Two- and Three-Dimensional Live Cell Imaging of DNA Damage Response Proteins
Published on: September 28, 2012
The Cdc14B-Cdh1-Plk1 axis controls the G2 DNA-damage-response checkpoint
Florian Bassermann1, David Frescas, Daniele Guardavaccaro
1Department of Pathology, NYU Cancer Institute, New York University School of Medicine, 550 First Avenue, MSB 599, New York, NY 10016, USA.
Cell
|July 30, 2008
Summary
Mammalian cells activate a DNA repair pathway in G2 phase after DNA damage. This involves Cdc14B phosphatase, leading to Plk1 degradation and stabilizing checkpoint proteins for an effective G2 DNA-damage response.
Area of Science:
- Cell Biology
- Molecular Biology
- Genetics
Background:
- Mammalian cells require robust mechanisms to prevent entry into mitosis following DNA damage during the G2 phase.
- The G2 DNA-damage response (DDR) checkpoint is critical for maintaining genomic stability by halting cell-cycle progression.
- Key regulators of mitosis and the cell cycle must be tightly controlled to ensure proper DNA repair.
Purpose of the Study:
- To elucidate the molecular pathway governing the G2 DNA-damage response in mammalian cells.
- To identify the role of the phosphatase Cdc14B in coordinating cell-cycle arrest and DNA repair.
- To understand how mitotic kinases and checkpoint proteins are regulated during genotoxic stress in G2.
Main Methods:
- Investigated the subcellular localization and activity of Cdc14B in response to genotoxic stress.
- Utilized biochemical assays to analyze the activation of the anaphase-promoting complex/cyclosome (APC/C(Cdh1)).
- Examined the degradation of mitotic kinase Plk1 and the stabilization of Claspin and Wee1.
- Assessed the role of the deubiquitylating enzyme Usp28 in regulating Claspin stability and Chk1 activation.
Main Results:
- Cdc14B translocates to the nucleoplasm from the nucleolus upon genotoxic stress in G2.
- Cdc14B activation of APC/C(Cdh1) leads to Plk1 degradation, stabilizing Claspin and Wee1 for an efficient G2 checkpoint.
- Usp28 counteracts APC/C(Cdh1)-mediated Claspin degradation, ensuring Chk1 activation for DNA repair.
Conclusions:
- A novel pathway involving Cdc14B, APC/C(Cdh1), and Usp28 is essential for the G2 DNA-damage response.
- This pathway ensures cell-cycle arrest and facilitates DNA repair by regulating key mitotic and checkpoint proteins.
- The findings provide critical insights into maintaining genomic integrity following DNA damage.
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