The role of DNA‐PK in aging and energy metabolism.

DNA‐dependent protein kinase (DNA‐PK) is a very large holoenzyme comprised of the p470 kDa DNA‐PK catalytic subunit (DNA‐PKcs) and the Ku heterodimer consisting of the p86 (Ku 80) and p70 (Ku 70) subunits. It is best known for its nonhomologous end joining (NHEJ) activity, which repairs double‐strand DNA (dsDNA) breaks (DSBs). As expected, the absence of DNA‐PK activity results in sensitivity to ionizing radiation, which generates DSBs and defect in lymphocyte development, which requires NHEJ of the V(D)J region in the immunoglobulin and T‐cell receptor loci. DNA‐PK also has been reported to have functions seemingly unrelated to NHEJ. For example, DNA‐PK responds to insulin signaling to facilitate the conversion of carbohydrates to fatty acids in the liver. More recent evidence indicates that DNA‐PK activity increases with age in skeletal muscle, promoting mitochondrial loss and weight gain. These discoveries suggest that our understanding of DNA‐PK is far from complete. As many excellent reviews have already been written about the role of DNA‐PK in NHEJ, here we will review the non‐NHEJ role of DNA‐PK with a focus on its role in aging and energy metabolism. [ABSTRACT FROM AUTHOR]

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