The multifaceted functions of DNA-PKcs: implications for the therapy of human diseases

Jinghong Wu1, Liwei Song2, Mingjun Lu1

  • 1Cancer Research Center Beijing Chest Hospital Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Research Institute Beijing China.

Medcomm
|June 20, 2024
PubMed

Insights

DNA-dependent protein kinase (DNA-PKcs) is crucial for DNA repair and has diverse roles in immunity and development. Understanding DNA-PKcs

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Biochemistry

Background:

  • DNA-dependent protein kinase (DNA-PK), catalytic subunit (DNA-PKcs), forms the DNA-PK holoenzyme with Ku70/Ku80.
  • This holoenzyme initiates nonhomologous end joining (NHEJ) for DNA double-strand break (DSB) repair.
  • DNA-PKcs is vital for DNA end processing and joining during NHEJ.

Purpose of the Study:

  • To review the multifaceted roles of DNA-PKcs in human diseases.
  • To discuss the therapeutic potential of DNA-PKcs inhibitors in clinical trials.
  • To provide insights into DNA-PKcs-associated diseases.

Main Methods:

  • Literature review of DNA-PKcs functions and disease associations.
  • Analysis of preclinical data on DNA-PKcs inhibitors in cancer treatment.
  • Discussion of current progress in clinical trials for DNA-PKcs inhibitors.

Main Results:

  • DNA-PKcs has diverse functions beyond DSB repair, including roles in V(D)J recombination, class switch recombination (CSR), and innate immunity.
  • DNA-PKcs deficiency is linked to neurological, cancer, and immunological disorders.
  • DNA-PKcs inhibitors show promise in preclinical cancer models.

Conclusions:

  • DNA-PKcs plays a critical role in maintaining genomic stability and has broader biological functions.
  • Targeting DNA-PKcs presents a promising therapeutic strategy for various diseases, particularly cancer.
  • Further research into DNA-PKcs inhibitors is warranted for clinical application.

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