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

Chengming Zhu, Molly A. Bogue, Dae Sik Lim, Paul Hasty, David B. Roth

Research output: Contribution to journalArticlepeer-review

372 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)379-389
Number of pages11
JournalCell
Volume86
Issue number3
DOIs
StatePublished - Aug 9 1996

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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