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Continuous Fluorescence-Based Endonuclease-Coupled DNA Methylation Assay to Screen for DNA Methyltransferase Inhibitors

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Specific inhibition of DNMT1/CFP1 reduces cancer phenotypes and enhances chemotherapy effectiveness

Mathilde Cheray¹, Arulraj Nadaradjane, Pascal Bonnet

¹UMR 892 INSERM, 6299 CNRS, Nantes, France.

|August 12, 2014

Abstract

Aim:

DNA methylation is a fundamental biologic process of genomes and is a candidate for pharmacological manipulation that might have important therapeutic advantages. Thus, DNA methyltransferases (DNMTs) appear to be ideal targets for drug intervention.

Materials & Methods:

To develop a new generation of DNMT inhibitor, we analyzed the ability of peptides to selectively inhibit certain DNMT1-incuding complexes.

Results:

Our study demonstrates that the disruption of DNMT1/CFP1-including complexes increases the efficiency of chemotherapeutic treatment on established tumors in mice.

Conclusion:

Our data opens a promising and innovative alternative to the development of DNMT inhibitors.

Keywords:

DNA methylation DNMT inhibitor DNMT1 cell death epigenetic glioblastoma glioma

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