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DNA-Dependent Protein Kinase Catalytic Subunit (DNA-PKcs): Beyond the DNA Double-Strand Break Repair
Ye-Rim Lee1, Gi-Sue Kang1, Taerim Oh1
1College of Veterinary Medicine, Seoul National University, Seoul 08826, Korea.
Molecules and Cells
|February 9, 2023
Summary
DNA-dependent protein kinase catalytic subunit (DNA-PKcs) repairs DNA double-strand breaks and impacts immune cell development. Emerging research reveals its novel cytoplasmic roles in metabolism and cytokine production, complicating therapeutic targeting.
Area of Science:
- Molecular Biology
- Cellular Biology
- Immunology
Background:
- DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is crucial for DNA double-strand break repair via non-homologous end joining.
- DNA-PKcs plays vital roles in T and B cell development through V(D)J and class switch recombination, respectively.
- Defects in these DNA repair pathways can lead to severe combined immunodeficiency (SCID).
Purpose of the Study:
- To highlight recent findings on the novel functions and subcellular localization of DNA-PKcs.
- To emphasize the importance of selecting appropriate experimental models for studying DNA-PKcs.
- To discuss the implications of DNA-PKcs's multifaceted roles in cellular processes and potential therapeutic interventions.
Main Methods:
- Review of recent scientific literature and experimental evidence.
- Analysis of studies investigating DNA-PKcs localization and function in different cellular contexts.
- Consideration of data from both defective DNA-PKcs cells and DNA-PKcs knockout models.
Main Results:
- DNA-PKcs has been observed in both the nucleus and cytoplasm.
- Cytoplasmic DNA-PKcs phosphorylates proteins involved in cellular metabolism and cytokine production.
- Experimental evidence for DNA-PKcs function can differ between defective and knockout cell models.
Conclusions:
- DNA-PKcs exhibits novel extranuclear functions beyond DNA repair, impacting cellular metabolism and immunity.
- Careful selection of experimental models is essential due to variations in observed DNA-PKcs activity.
- The complex roles and localization of DNA-PKcs may complicate the effects of its inhibitors in clinical trials for cancer therapy.
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