DNA-PKcs

DNA-dependent protein kinase, catalytic subunit, also known as DNA-PKcs, is an is_associated_with::enzyme that in humans is encoded by the PRKDC is_associated_with::gene. DNA-PKcs belongs to the is_associated_with::phosphatidylinositol 3-kinase-related kinase protein family.

Function
DNA-PKcs is the catalytic subunit of a nuclear DNA-dependent serine/threonine protein kinase called DNA-PK. The second component is the autoimmune antigen Ku. On its own, DNA-PKcs is inactive and relies on Ku to direct it to DNA ends and trigger its kinase activity. DNA-PKcs is required for the is_associated_with::non-homologous end joining (NHEJ) pathway of is_associated_with::DNA repair, which rejoins double-strand breaks. It is also required for is_associated_with::V(D)J recombination, a process that utilizes NHEJ to promote immune system diversity. DNA-PKcs knockout mice have severe combined immunodeficiency due to their V(D)J recombination defect.

Many proteins have been identified as substrates for the kinase activity of DNA-PK. Autophosphorylation of DNA-PKcs appears to play a key role in NHEJ and is thought to induce a conformational change that allows end processing enzymes to access the ends of the double-strand break. DNA-PK also cooperates with ATR and ATM to phosphorylate proteins involved in the DNA damage checkpoint.

Aging
is_associated_with::Non-homologous end joining (NHEJ) is the principal DNA repair process used by mammalian is_associated_with::somatic cells to cope with double-strand breaks that continually occur in the genome. DNA-PKcs is one of the key components of the NHEJ machinery. DNA-PKcs deficient mice have a shorter lifespan and show an earlier onset of numerous aging related pathologies than corresponding wild-type littermates. These findings suggest that failure to efficiently repair DNA double-strand breaks results in premature aging, consistent with the is_associated_with::DNA damage theory of aging. (See also Bernstein et al. )

Interactions
DNA-PKcs has been shown to interact with:


 * ATM,
 * is_associated_with::C1D, and
 * is_associated_with::CDC5L,
 * is_associated_with::CHEK1,
 * is_associated_with::CHUK,
 * is_associated_with::CIB1,
 * is_associated_with::DCLRE1C,
 * is_associated_with::ILF2,
 * is_associated_with::ILF3,
 * is_associated_with::Ku80,
 * is_associated_with::NCOA6,
 * is_associated_with::P53,
 * is_associated_with::RPA2, and
 * WRN.