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DNA-PKcs: A Multi-Faceted Player in DNA Damage Response.

Xiaoqiao Yue1,2, Chenjun Bai2, Dafei Xie2

  • 1School of Public Health, University of South China, Hengyang, China.

Frontiers in Genetics
|January 11, 2021
PubMed
Summary

DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is vital for DNA repair and genomic stability. Targeting DNA-PKcs offers a promising strategy for enhancing cancer radiotherapy efficacy.

Keywords:
DNA damage responseDNA repairDNA-PKcsgenomic instabilityradiosensitization

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Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is a key kinase in the phosphatidylinositol 3-kinase-related kinase family.
  • DNA-PKcs forms the DNA-PK holoenzyme with Ku80/Ku70, playing critical roles in the cellular DNA damage response (DDR).

Purpose of the Study:

  • To elucidate the multifaceted roles of DNA-PKcs in cellular responses to DNA damage.
  • To highlight the therapeutic potential of targeting DNA-PKcs in cancer treatment, particularly in combination with radiotherapy.

Main Methods:

  • The study reviews the known functions and mechanisms of DNA-PKcs in DNA double-strand break (DSB) repair and other cellular processes.
  • It discusses the regulation of DNA-PKcs activity and its involvement in various DDR pathways.

Main Results:

  • DNA-PKcs is rapidly recruited to DSB sites and activated through auto-phosphorylation and phosphorylation by ATM.
  • It regulates critical DDR pathways including Non-Homologous End Joining (NHEJ) repair, replication stress response, cell cycle checkpoints, and telomere maintenance.

Conclusions:

  • Precise regulation of DNA-PKcs complex formation and activity is essential for maintaining genomic stability.
  • Inhibiting DNA-PKcs presents a promising strategy for developing novel radiosensitizers and cancer therapeutics to enhance radiotherapy outcomes.