scholarly journals DNA-dependent protein kinase catalytic subunit: A relative of phosphatidylinositol 3-kinase and the ataxia telangiectasia gene product

Cell ◽  
1995 ◽  
Vol 82 (5) ◽  
pp. 849-856 ◽  
Author(s):  
Katharine O Hartley ◽  
David Gell ◽  
Graeme C.M Smith ◽  
Hong Zhang ◽  
Nullin Divecha ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Gene Product ◽  
Ataxia Telangiectasia ◽  
Catalytic Subunit ◽  
Phosphatidylinositol 3 Kinase ◽  
Dependent Protein Kinase ◽  
Subunit A ◽  
Dependent Protein ◽  
Phosphatidylinositol 3

scholarly journals Stretch and Twist of HEAT Repeats Leads to Activation of DNA-PK Kinase

2020 ◽  
Author(s):  
Xuemin Chen ◽  
Xiang Xu ◽  
Yun Chen ◽  
Joyce C. Cheung ◽  
Huaibin Wang ◽  
...  
Keyword(s):  
Protein Kinase ◽  
General Feature ◽  
Structural Plasticity ◽  
Catalytic Subunit ◽  
Phosphatidylinositol 3 Kinase ◽  
Dependent Protein Kinase ◽  
Existing Structures ◽  
Repeat Proteins ◽  
Dependent Protein ◽  
Stress Signals

AbstractPhosphatidylinositol 3-kinase-related kinases (PIKKs) are composed of conserved FAT and kinase domains (FATKIN) along with varied solenoid structures made of HEAT repeats. These kinases are activated in response to cellular stress signals, but the mechanisms governing activation and regulation remain unresolved. For DNA-dependent protein kinase (DNA-PK), all existing structures represent inactive states with resolution limited to 4.3 Å at best. Here we report the cryoEM structures of DNA-PKcs (catalytic subunit) bound to a DNA end, or complexed with Ku70/80 and DNA, in both inactive and activated forms at resolutions of 3.7 Å overall, and 3.2 Å for FATKIN. These structures reveal the sequential transition of DNA-PK from inactive to activated forms. Most notably, activation of the kinase involves previously unknown stretching and twisting within individual solenoid segments and coordinated shifts of neighboring segments in opposite directions. This unprecedented structural plasticity of helical repeats may be a general feature of HEAT-repeat proteins.

scholarly journals DNA-dependent protein kinase catalytic subunit: a target for an ICE-like protease in apoptosis.

1996 ◽  
Vol 15 (13) ◽  
pp. 3238-3246 ◽  
Author(s):  
Q. Song ◽  
S. P. Lees-Miller ◽  
S. Kumar ◽  
Z. Zhang ◽  
D. W. Chan ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Catalytic Subunit ◽  
Dependent Protein Kinase ◽  
Subunit A ◽  
Dependent Protein

scholarly journals Potential Role of Phosphatidylinositol 3 Kinase, rather than DNA-dependent Protein Kinase, in CpG DNA–induced Immune Activation

2002 ◽  
Vol 196 (2) ◽  
pp. 269-274 ◽  
Author(s):  
Ken J. Ishii ◽  
Fumihiko Takeshita ◽  
Ihsan Gursel ◽  
Mayda Gursel ◽  
Jacqueline Conover ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Cell Activation ◽  
Critical Role ◽  
Phosphatidylinositol 3 Kinase ◽  
Dependent Protein Kinase ◽  
Cpg Dna ◽  
Dependent Cell ◽  
Dependent Protein ◽  
Stimulation Current ◽  
Phosphatidylinositol 3

Unmethylated CpG motifs present in bacterial DNA stimulate a strong innate immune response. There is evidence that DNA-dependent protein kinase (DNA-PK) mediates CpG signaling. Specifically, wortmannin (an inhibitor of phosphatidylinositol 3 kinase [PI3]-kinases including DNA-PK) interferes with CpG-dependent cell activation, and DNA-PK knockout (KO) mice fail to respond to CpG stimulation. Current studies establish that wortmannin actually inhibits the uptake and colocalization of CpG DNA with toll-like receptor (TLR)-9 in endocytic vesicles, thereby preventing CpG-induced activation of the NF-κB signaling cascade. We find that DNA-PK is not involved in this process, since three strains of DNA-PK KO mice responded normally to CpG DNA. These results support a model in which CpG signaling is mediated through TLR-9 but not DNA-PK, and suggest that wortmannin-sensitive member(s) of the PI3-kinase family play a critical role in shuttling CpG DNA to TLR-9.

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

Genes ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 1143
Author(s):  
Yoshihisa Matsumoto ◽  
Anie Day D. C. Asa ◽  
Chaity Modak ◽  
Mikio Shimada
Keyword(s):  
Protein Kinase ◽  
Ataxia Telangiectasia ◽  
Catalytic Subunit ◽  
Nonhomologous End Joining ◽  
Dna Double Strand Breaks ◽  
Ataxia Telangiectasia Mutated ◽  
End Joining ◽  
Dependent Protein Kinase ◽  
Strand Breaks ◽  
Dependent Protein

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.

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