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The role of DNA ‐ PK in aging and energy metabolism
Author(s) -
Chung Jay H.
Publication year - 2018
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.14410
Subject(s) - dna , ku80 , dna repair , biochemistry , biology , microbiology and biotechnology , chemistry , gene , dna binding protein , transcription factor
DNA ‐dependent protein kinase ( DNA ‐ PK ) is a very large holoenzyme comprised of the p470 kDa DNA ‐ PK catalytic subunit ( DNA ‐ PK cs ) 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 (ds DNA ) breaks ( DSB s). As expected, the absence of DNA ‐ PK activity results in sensitivity to ionizing radiation, which generates DSB s 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.