Ku86-Deficient Mice Exhibit Severe Combined Immunodeficiency and Defective Processing of V(D)J Recombination Intermediates

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-defici...

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Bibliographic Details
Published in:Cell 1996-08, Vol.86 (3), p.379-389
Main Authors: Zhu, Chengming, Bogue, Molly A, Lim, Dae-Sik, Hasty, Paul, Roth, David B
Format: Article
Language:English
Subjects:
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
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Summary: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.
ISSN:0092-8674
1097-4172
DOI:10.1016/S0092-8674(00)80111-7