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Updated: Jan 27, 2026
12:26
Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay
Published on: May 3, 2018
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New Phosphorylation Sites of Rad51 by c-Met Modulates Presynaptic Filament Stability
Thomas Chabot1, Alain Defontaine2, Damien Marquis3
1Group of Mechanism and Regulation of DNA Repair, UFIP UMR CNRS 6286/University of Nantes, 44322 Nantes, France. thomas.chabot1@univ-nantes.fr.
Cancers
|March 27, 2019
Summary
The c-MET receptor tyrosine kinase phosphorylates the RAD51 DNA repair protein, enhancing its stability. This discovery reveals a new mechanism in cancer
Area of Science:
- Molecular Biology
- Cancer Research
- DNA Repair Mechanisms
Background:
- Genomic instability, driven by faulty DNA repair, initiates cancer and causes treatment resistance.
- Homologous Recombination (HR) is a critical DNA repair pathway involving the RAD51 protein.
- Receptor tyrosine kinases (RTKs), including c-MET, are implicated in regulating HR.
Purpose of the Study:
- To investigate the direct relationship between the c-MET receptor tyrosine kinase and RAD51.
- To elucidate the role of c-MET in regulating the Homologous Recombination DNA repair pathway.
Main Methods:
- In vitro biochemical assays to assess c-MET's phosphorylation of RAD51.
- Analysis of RAD51 phosphorylation sites.
- Assessment of RAD51 filament stability in the presence of the BRCA2 BRC peptide.
Main Results:
- Demonstrated that c-MET directly phosphorylates RAD51 on four tyrosine residues.
- Phosphorylation does not impede RAD51 presynaptic filament formation.
- c-MET-mediated phosphorylation enhances RAD51 filament stability against BRCA2 inhibition.
Conclusions:
- c-MET plays a significant role in the DNA damage response by phosphorylating RAD51.
- These post-translational modifications regulate the interaction between BRCA2 and RAD51.
- Understanding this c-MET-RAD51 axis is crucial for developing novel cancer therapies.
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