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A targeted DNA-PKcs-null mutation reveals DNA-PK-independent functions for KU in V(D)J recombination.

Immunity | Sep 28, 1998

http://www.ncbi.nlm.nih.gov/pubmed/9768756

The DNA-dependent protein kinase (DNA-PK) consists of Ku70, Ku80, and a large catalytic subunit, DNA-PKcs. Targeted inactivation of the Ku70 or Ku80 genes results in elevated ionizing radiation (IR) sensitivity and inability to perform both V(D)J coding-end and signal (RS)-end joining in cells, with severe growth retardation plus immunodeficiency in mice. In contrast, we now demonstrate that DNA-PKcs-null mice generated by gene-targeted mutation, while also severely immunodeficient, exhibit no growth retardation. Furthermore, DNA-PKcs-null cells are blocked for V(D)J coding-end joining, but retain normal RS-end joining. Finally, while DNA-PK-null fibroblasts exhibited increased IR sensitivity, DNA-PKcs-deficient ES cells did not. We conclude that Ku70 and Ku80 may have functions in V(D)J recombination and DNA repair that are independent of DNA-PKcs.

Pubmed ID: 9768756 RIS Download

Mesh terms: Animals | Antigens, Nuclear | DNA Helicases | DNA-Activated Protein Kinase | DNA-Binding Proteins | Embryo, Mammalian | Female | Fibroblasts | Gene Rearrangement, B-Lymphocyte, Heavy Chain | Gene Targeting | Immunoglobulin Joining Region | Male | Mice | Mice, Inbred C57BL | Mice, Knockout | Mutation | Nuclear Proteins | Phenotype | Protein-Serine-Threonine Kinases | Radiation, Ionizing | Severe Combined Immunodeficiency | Signal Transduction | Stem Cells | Thymus Gland

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Associated grants

  • Agency: NIAID NIH HHS, Id: AI20047
  • Agency: NIAID NIH HHS, Id: AI35714

Mouse Genome Informatics (Data, Gene Annotation)

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