Ku86-deficient mice exhibit severe combined immunodeficiency and defective processing of V(D)J recombination intermediates

Cell. 1996 Aug 9;86(3):379-89. doi: 10.1016/s0092-8674(00)80111-7.

Abstract

Ku is a heterodimeric DNA end binding complex composed of 70 and 86 kDa subunits. Here, we show that Ku86 is essential for normal V(D)J recombination in vivo, as Ku86-deficient mice are severely defective for formation of coding joints. Unlike severe combined immunodeficient (scid) mice, Ku86-deficient mice are also defective for signal joint formation. Both hairpin coding ends and blunt full-length signal ends accumulate. Contrary to expectation, Ku86 is evidently not required for protection of either type of V(D)J recombination intermediate. Instead, V(D)J recombination appears to be arrested after the cleavage step in Ku86-deficient mice. We suggest that Ku86 may be required to remodel or disassemble DNA-protein complexes containing broken ends, making them available for further processing and joining.

Publication types

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

MeSH terms

  • Animals
  • Antigens, Nuclear*
  • B-Lymphocytes / cytology
  • Base Sequence
  • Cell Differentiation
  • DNA Helicases*
  • DNA Primers
  • DNA Repair
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology*
  • Gene Rearrangement, T-Lymphocyte / genetics*
  • Ku Autoantigen
  • Mice
  • Mice, SCID
  • Molecular Sequence Data
  • Nuclear Proteins / genetics
  • Nuclear Proteins / physiology*
  • Nucleic Acid Conformation
  • Polymerase Chain Reaction
  • Restriction Mapping
  • Severe Combined Immunodeficiency / enzymology
  • Severe Combined Immunodeficiency / genetics*
  • T-Lymphocytes / cytology

Substances

  • Antigens, Nuclear
  • DNA Primers
  • DNA-Binding Proteins
  • Nuclear Proteins
  • DNA Helicases
  • XRCC5 protein, human
  • Xrcc5 protein, mouse
  • Xrcc6 protein, human
  • Xrcc6 protein, mouse
  • Ku Autoantigen

Associated data

  • GENBANK/X66323