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

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.

journal_name

Cell

journal_title

Cell

authors

Zhu C,Bogue MA,Lim DS,Hasty P,Roth DB

doi

10.1016/s0092-8674(00)80111-7

subject

Has Abstract

pub_date

1996-08-09 00:00:00

pages

379-89

issue

3

eissn

0092-8674

issn

1097-4172

pii

S0092-8674(00)80111-7

journal_volume

86

pub_type

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