Small-Molecule Inhibition of CBX4/7 Hypersensitises Homologous Recombination-Impaired Cancer to Radiation by Compromising CtIP-Mediated DNA End Resection
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Cell Culture
2.2. Plasmids and Transfection
2.3. Compounds Used in Biological Assays
2.4. Plasmid Re-Joining Assays
2.5. Flow Cytometry
2.6. Live-Cell Imaging
2.7. High-Content Screening and Immunofluorescence
2.7.1. Image Acquisition and Analysis
2.7.2. Manual Counting
2.8. Antibodies for Immunofluorescence
2.9. Statistical Analysis
3. Results
3.1. UNC3866 Decreases DNA End Resection Efficiency
3.2. UNC3866 Reduces End-Resection-Dependent Repair Efficiency
3.3. UNC3866 Selectively Sensitises HR-Deficient Cells to IR
3.4. UNC3866 Sensitivity Might Derive from Alt-EJ Inhibition Rather Than Replication Fork Destabilisation
3.5. UNC3866 Reduces RAD51 Foci Formation in OVCAR3 Cells
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Osborne, H.C.; Foster, B.M.; Al-Hazmi, H.; Meyer, S.; Larrosa, I.; Schmidt, C.K. Small-Molecule Inhibition of CBX4/7 Hypersensitises Homologous Recombination-Impaired Cancer to Radiation by Compromising CtIP-Mediated DNA End Resection. Cancers 2024, 16, 2155. https://doi.org/10.3390/cancers16112155
Osborne HC, Foster BM, Al-Hazmi H, Meyer S, Larrosa I, Schmidt CK. Small-Molecule Inhibition of CBX4/7 Hypersensitises Homologous Recombination-Impaired Cancer to Radiation by Compromising CtIP-Mediated DNA End Resection. Cancers. 2024; 16(11):2155. https://doi.org/10.3390/cancers16112155
Chicago/Turabian StyleOsborne, Hugh C., Benjamin M. Foster, Hazim Al-Hazmi, Stefan Meyer, Igor Larrosa, and Christine K. Schmidt. 2024. "Small-Molecule Inhibition of CBX4/7 Hypersensitises Homologous Recombination-Impaired Cancer to Radiation by Compromising CtIP-Mediated DNA End Resection" Cancers 16, no. 11: 2155. https://doi.org/10.3390/cancers16112155