Increased Resection at DSBs in G2-Phase Is a Unique Phenotype Associated with DNA-PKcs Defects That Is Not Shared by Other Factors of c-NHEJ
Abstract
:1. Introduction
2. Materials and Methods
2.1. Cell Culture
2.2. Irradiation
2.3. Treatment of Cell Cultures with Inhibitors
2.4. RNA Interference
2.5. Quantitative Image-Based Cytometry (QIBC) Analysis by Indirect Immunofluorescence (IF)
2.6. Flow Cytometry (FC) Analysis of DNA End-Resection by RPA70 Quantification
2.7. Polyacrylamide Gel Electrophoresis (SDS-PAGE) and Western Blot Analysis
2.8. Cytogenetic Analysis of Translocation Formation in Cells Irradiated in G2-Phase
2.9. Statistical Analysis
3. Results
3.1. Specific Analysis of Resection in G2-Phase Cells That Are also Irradiated in G2-Phase
3.2. Genetic Ablation of DNA-PKcs Causes Hyper-Resection in Cells Irradiated in G2-Phase
3.3. Inhibition of DNA-PKcs Using Small Molecule Inhibitors Fails to Cause Hyper-Resection
3.4. The Curtailing Function of DNA-PKcs in Resection Is Independent of Ku
3.5. Defects in Factors of c-NHEJ, Other Than DNA-PKcs, Fail to Cause Hyper-Resection at DSBs
3.6. Hyper-Resection in DNA-PKcs Mutants Causes an Explosion in Chromosomal Translocation Formation
3.7. Factors Involved in DNA End Resection in the Absence of DNA-PKcs
4. Discussion
4.1. Genetic Ablation of DNA-PKcs Causes Hyper-Resection in Cells Irradiated in G2-Phase
4.2. Integration of DNA-PKcs Functions with ATM and ATR Functions
4.3. DNA-PKcs Is a Candidate Regulator of HR with Decreasing IR Dose
4.4. A model of DNA-PKcs Function in DSB Repair Pathway Choice at Low DSB Loads
5. Outlook
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Xiao, H.; Li, F.; Mladenov, E.; Soni, A.; Mladenova, V.; Pan, B.; Dueva, R.; Stuschke, M.; Timmermann, B.; Iliakis, G. Increased Resection at DSBs in G2-Phase Is a Unique Phenotype Associated with DNA-PKcs Defects That Is Not Shared by Other Factors of c-NHEJ. Cells 2022, 11, 2099. https://doi.org/10.3390/cells11132099
Xiao H, Li F, Mladenov E, Soni A, Mladenova V, Pan B, Dueva R, Stuschke M, Timmermann B, Iliakis G. Increased Resection at DSBs in G2-Phase Is a Unique Phenotype Associated with DNA-PKcs Defects That Is Not Shared by Other Factors of c-NHEJ. Cells. 2022; 11(13):2099. https://doi.org/10.3390/cells11132099
Chicago/Turabian StyleXiao, Huaping, Fanghua Li, Emil Mladenov, Aashish Soni, Veronika Mladenova, Bing Pan, Rositsa Dueva, Martin Stuschke, Beate Timmermann, and George Iliakis. 2022. "Increased Resection at DSBs in G2-Phase Is a Unique Phenotype Associated with DNA-PKcs Defects That Is Not Shared by Other Factors of c-NHEJ" Cells 11, no. 13: 2099. https://doi.org/10.3390/cells11132099
APA StyleXiao, H., Li, F., Mladenov, E., Soni, A., Mladenova, V., Pan, B., Dueva, R., Stuschke, M., Timmermann, B., & Iliakis, G. (2022). Increased Resection at DSBs in G2-Phase Is a Unique Phenotype Associated with DNA-PKcs Defects That Is Not Shared by Other Factors of c-NHEJ. Cells, 11(13), 2099. https://doi.org/10.3390/cells11132099