Ku80

Ku80 is a is_associated_with::protein that, in humans, is encoded by the XRCC5 is_associated_with::gene. Together, is_associated_with::Ku70 and Ku80 make up the Ku heterodimer, which binds to is_associated_with::DNA double-strand break ends and is required for the is_associated_with::non-homologous end joining (NHEJ) pathway of is_associated_with::DNA repair. It is also required for is_associated_with::V(D)J recombination, which utilizes the NHEJ pathway to promote antigen diversity in the mammalian is_associated_with::immune system.

In addition to its role in NHEJ, Ku is required for telomere length maintenance and subtelomeric gene silencing.

Ku was originally identified when patients with is_associated_with::systemic lupus erythematosus were found to have high levels of autoantibodies to the protein.

Nomenclature
Ku80 has been referred to by several names including:
 * Lupus Ku autoantigen protein p80
 * ATP-dependent DNA helicase 2 subunit 2
 * X-ray repair complementing defective repair in Chinese hamster cells 5
 * X-ray repair cross-complementing 5 (XRCC5)

Clinical significance
A rare microsatellite polymorphism in this gene is associated with cancer in patients of varying is_associated_with::radiosensitivity.

Interactions
Ku80 has been shown to interact with:


 * is_associated_with::DNA-PKcs,
 * is_associated_with::GCN5L2,
 * is_associated_with::Ku70,
 * is_associated_with::NCOA6,
 * is_associated_with::PCNA,
 * is_associated_with::POU2F1,
 * is_associated_with::TERF2IP,
 * is_associated_with::Telomerase reverse transcriptase,
 * is_associated_with::Tyrosine kinase 2, and
 * is_associated_with::Werner syndrome ATP-dependent helicase.

Senescence
Mouse mutants with homozygous defects in Ku80 experience an early onset of is_associated_with::senescence. Ku80(-/-) mice exhibit aging-related pathology (osteopenia, atrophic skin, hepatocellular degeneration, hepatocellular inclusions, hepatic hyperplastic foci and age-specific mortality). Furthermore, Ku80(-/-) mice exhibit severely reduced lifespan and size. Loss of only a single Ku80 allele in Ku(-/+) heterozygous mice causes accelerated aging in skeletal muscle, although post natal growth is normal. An analysis of the level of Ku80 protein in human, cow, and mouse indicated that Ku80 levels vary dramatically between species, and that these levels are strongly correlated with species longevity. These results suggest that the NHEJ pathway of DNA repair mediated by Ku80 plays a significant role in repairing double-strand breaks that would otherwise cause early senescence (see is_associated_with::DNA damage theory of aging).