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DNA mimic foldamers affect chromatin composition and disturb cell cycle progression
Vera Kleene1, Valentina Corvaglia2, Erika Chacin1
1Department of Molecular Biology, Biomedical Center Munich, Faculty of Medicine, Ludwig-Maximilians University, Großhaderner Strasse 9, 82152 Planegg-Martinsried, Germany.
Nucleic Acids Research
|August 31, 2023
Summary
Synthetic foldamers, DNA mimics, disrupt the origin recognition complex, affecting cell cycle progression. These molecules offer a novel approach to targeting chromatin-associated proteins for therapeutic development.
Area of Science:
- Biochemistry
- Molecular Biology
- Pharmacology
Background:
- Synthetic foldamers mimicking DNA charge surfaces can modulate protein-DNA interactions.
- Understanding their impact on complex chromatin is crucial for pharmacological applications.
Purpose of the Study:
- To investigate the influence of DNA mimic foldamers on the chromatin-bound proteome.
- To assess the pharmacological potential and specificity of these foldamers.
Main Methods:
- Systematic study using an in vitro chromatin assembly extract.
- In vitro and in vivo experiments to assess foldamer effects on protein-DNA interactions and cell cycle.
Main Results:
- Foldamers efficiently interfere with the chromatin association of the origin recognition complex (ORC).
- This interference leads to cell cycle disturbances in treated cells.
- Direct interaction between foldamers and ORC causes failure in organizing chromatin around replication origins.
Conclusions:
- DNA mimic foldamers are effective tools for altering chromatin assembly.
- They can selectively interfere with biological mechanisms, offering therapeutic design possibilities.
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