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Target intelligence / Profile preview
DNA-dependent Protein Kinase Catalytic Subunit (DNA-PKcs)
- Target
- DNA-PKcs
- Molecular classification
- PIKK, Serine/threonine protein kinase, Enzyme
01
Overview
DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is a large serine/threonine protein kinase that plays a central role in the repair of DNA double-strand breaks (DSBs). It is part of the phosphatidylinositol 3-kinase-related kinase (PIKK) family and forms an active holoenzyme with the Ku70/Ku80 heterodimer. DNA-PKcs is essential for NHEJ, V(D)J recombination, and apoptosis regulation. Defects lead to SCID, while overexpression is linked to cancer progression and therapy resistance. Several small-molecule inhibitors are under clinical investigation to target DNA-PKcs and enhance the efficacy of cancer therapies.
- Other names
- PRKDC
02
Mechanism of action
Inhibition of DNA-PKcs prevents efficient repair of therapy-induced DSBs, sensitizing tumors to treatment.
03
Biological functions
Non-homologous end joining (NHEJ)V(D)J RecombinationApoptosis RegulationTelomere maintenanceCell cycle progressionInnate immune responses
04
Disease associations
Severe combined immunodeficiency (SCID)CancerRadiotherapy/chemotherapy resistance
05
Safety considerations
Inhibition can impair DNA repair in normal tissues, leading to toxicity.Potential for off-target effects due to kinase similarity with other PIKK family members.Development of resistance mechanisms in cancer cells.
06
Interacting drugs
Small-molecule inhibitors (various, under clinical investigation)
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