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 kD a subunits. Here, we show that Ku86 is essential for normal V(D)J reco mbination in vivo, as Ku86-deficient mice are severely defective for f ormation of coding joints. Unlike severe combined immunodeficient (sci d) mice, Ku8B-deficient mice are also defective for signal joint forma tion. Both hairpin coding ends and blunt full-length signal ends accum ulate. Contrary to expectation, Ku86 is evidently not required for pro tection of either type of V(D)J recombination intermediate. Instead, V (D)J recombination appears to be arrested after the cleavage step in K u86-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.