Requirement for Ku80 in growth and immunoglobulin V(D)J recombination

Nature. 1996 Aug 8;382(6591):551-5. doi: 10.1038/382551a0.

Abstract

The DNA-dependent protein kinase (DNA-PK) is a mammalian serine/threonine kinase that is implicated in the repair of DNA double-strand breaks, DNA replication, transcription, and V(D)J recombination. To determine the role of the DNA-binding subunit of DNA-PK in vivo, we targeted Ku80 in mice. In mutant mice, T and B lymphocyte development is arrested at early progenitor stages and there is a profound deficiency in V(D)J rearrangement. Although Ku80-/- mice are viable and reproduce, they are 40-60% of the size of littermate controls. Consistent with this growth defect, fibroblasts derived from Ku80-/- embryos showed an early loss of proliferating cells, a prolonged doubling time, and intact cell-cycle checkpoints that prevented cells with damaged DNA from entering the cell-cycle. The unexpected growth phenotype suggests a new and important link between Ku80 and growth control.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, Nuclear*
  • Base Sequence
  • Cell Cycle / physiology
  • Cell Division / physiology
  • Cell Line
  • DNA Helicases*
  • DNA Primers
  • DNA-Activated Protein Kinase
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology*
  • Fibroblasts / cytology
  • Gene Rearrangement*
  • Gene Rearrangement, B-Lymphocyte
  • Gene Rearrangement, T-Lymphocyte
  • Gene Targeting
  • Growth / physiology*
  • Ku Autoantigen
  • Lymphocytes / cytology
  • Mice
  • Mice, SCID
  • Molecular Sequence Data
  • Nuclear Proteins / genetics
  • Nuclear Proteins / physiology*
  • Phosphorylation
  • Protein-Serine-Threonine Kinases / metabolism

Substances

  • Antigens, Nuclear
  • DNA Primers
  • DNA-Binding Proteins
  • Nuclear Proteins
  • DNA-Activated Protein Kinase
  • Protein-Serine-Threonine Kinases
  • DNA Helicases
  • XRCC5 protein, human
  • Xrcc6 protein, human
  • Xrcc6 protein, mouse
  • Ku Autoantigen