DNA-Dependent Protein Kinase Catalytic Subunit: The Sensor for DNA Double-Strand Breaks Structurally and Functionally Related to Ataxia Telangiectasia Mutated.

Abstract

The DNA-dependent protein kinase (DNA-PK) is composed of a DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and Ku70/Ku80 heterodimer. DNA-PK is thought to act as the "sensor" for DNA double-stranded breaks (DSB), which are considered the most deleterious type of DNA damage. In particular, DNA-PKcs and Ku are shown to be essential for DSB repair through nonhomologous end joining (NHEJ). The phenotypes of animals and human individuals with defective DNA-PKcs or Ku functions indicate their essential roles in these developments, especially in neuronal and immune systems. DNA-PKcs are structurally related to Ataxia-telangiectasia mutated (ATM), which is also implicated in the cellular responses to DSBs. DNA-PKcs and ATM constitute the phosphatidylinositol 3-kinase-like kinases (PIKKs) family with several other molecules. Here, we review the accumulated knowledge on the functions of DNA-PKcs, mainly based on the phenotypes of DNA-PKcs-deficient cells in animals and human individuals, and also discuss its relationship with ATM in the maintenance of genomic stability.

• Authors: Yoshihisa Matsumoto, Anie Day D C Asa, Chaity Modak, Mikio Shimada
• Journal: Genes (Genes (Basel)) Vol. 12 Issue 8 (07 27 2021) ISSN: 2073-4425 [Electronic] Switzerland
• PMID: 34440313 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• ATM protein, human
• Ataxia Telangiectasia Mutated Proteins
• DNA-Activated Protein Kinase

Topics

• Ataxia Telangiectasia Mutated Proteins (metabolism)
• Catalytic Domain
• DNA Breaks, Double-Stranded
• DNA-Activated Protein Kinase (chemistry, metabolism)