Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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DNA-Dependent Protein Kinase Catalytic Subunit (DNA-PKcs): Beyond the DNA Double-Strand Break Repair

  • Ye-Rim Lee (College of Veterinary Medicine, Seoul National University) ;
  • Gi-Sue Kang (College of Veterinary Medicine, Seoul National University) ;
  • Taerim Oh (College of Veterinary Medicine, Seoul National University) ;
  • Hye-Ju Jo (College of Veterinary Medicine, Seoul National University) ;
  • Hye-Joon Park (College of Veterinary Medicine, Seoul National University) ;
  • G-One Ahn (College of Veterinary Medicine, Seoul National University)
  • Received : 2022.10.31
  • Accepted : 2022.11.09
  • Published : 2023.04.30
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Abstract

DNA-dependent protein kinase catalytic subunit (DNA-PKcs), a member of the phosphatidylinositol 3-kinase-related kinase family is a well-known player in repairing DNA double-strand break through non-homologous end joining pathway. This mechanism has allowed us to understand its critical role in T and B cell development through V(D)J recombination and class switch recombination, respectively. We have also learned that the defects in these mechanisms lead to the severely combined immunodeficiency (SCID). Here we highlight some of the latest evidence where DNA-PKcs has been shown to localize not only in the nucleus but also in the cytoplasm, phosphorylating various proteins involved in cellular metabolism and cytokine production. While it is an exciting time to unveil novel functions of DNA-PKcs, one should carefully choose experimental models to study DNA-PKcs as the experimental evidence has been shown to differ between cells of defective DNA-PKcs and those of DNA-PKcs knockout. Moreover, while there are several DNA-PK inhibitors currently being evaluated in the clinical trials in an attempt to increase the efficacy of radiotherapy or chemotherapy, multiple functions and subcellular localization of DNA-PKcs in various types of cells may further complicate the effects at the cellular and organismal level.

Keywords

Acknowledgement

This work was supported by the New Faculty Startup Fund from Seoul National University, the Research Institute for Veterinary Science, the Ministry of Science and Information, Communication, and Technology, Korea (RS-2022-00144495 and NRF-2020M2D9A2092374) and BK21 Four Future Veterinary Medicine Leading Education and Research Center, the Ministry of Education, Korea.

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