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DNA-Dependent Protein Kinase Catalytic Subunit: The Sensor for DNA Double-Strand Breaks Structurally and Functionally

Yoshihisa Matsumoto1, Anie Day D C Asa1, Chaity Modak1

  • 1Laboratory for Zero-Carbon Energy, Institute of Innovative Research, Tokyo Institute of Technology, Tokyo 152-8550, Japan.

Genes
|August 27, 2021
PubMed

Insights

DNA-dependent protein kinase (DNA-PK) senses DNA double-stranded breaks (DSB) and is crucial for their repair via nonhomologous end joining (NHEJ). Its deficiency impacts neuronal and immune systems, highlighting its role in genomic stability.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cell Biology

Background:

  • DNA-dependent protein kinase (DNA-PK) comprises DNA-PKcs and Ku70/Ku80, acting as a sensor for DNA double-stranded breaks (DSB).
  • DSBs are highly detrimental DNA lesions, and DNA-PK is critical for their repair through nonhomologous end joining (NHEJ).
  • Defects in DNA-PKcs or Ku lead to significant developmental issues, particularly in the nervous and immune systems.

Purpose of the Study:

  • To review the functions of DNA-PKcs.
  • To analyze phenotypes of DNA-PKcs-deficient cells in animals and humans.
  • To discuss the relationship between DNA-PKcs and ATM in maintaining genomic stability.

Main Methods:

  • Literature review of existing studies on DNA-PKcs.
  • Analysis of phenotypic data from DNA-PKcs-deficient animal models and human individuals.
  • Comparative analysis of DNA-PKcs and ATM functions.

Main Results:

  • DNA-PKcs and Ku are essential for DSB repair via NHEJ.
  • Phenotypes of DNA-PKcs deficiency highlight critical roles in neuronal and immune development.
  • DNA-PKcs shares structural and functional similarities with ATM, both belonging to the PIKK family.

Conclusions:

  • DNA-PK plays a vital role in sensing and repairing DSBs, crucial for genomic stability.
  • The functions of DNA-PKcs are essential for proper development, especially in immune and neuronal systems.
  • Understanding DNA-PKcs and its relationship with ATM provides insights into maintaining genomic integrity.
Keywords:
Ataxia–telangiectasia mutated (ATM)DNA damage responseDNA double-stranded break (DSB)DNA-dependent protein kinase (DNA-PK)DNA-dependent protein kinase catalytic subunit (DNA-PKcs)Kuphosphatidylinositol 3-kinase-like kinase (PIKK)protein kinase

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