Requirement for Ku80 in growth and immunoglobulin V(D)J recombination Journal Article

  


Authors: Nussenzweig, A.; Chen, C.; da Costa Soares, V.; Sanchez, M.; Sokol, K.; Nussenzweig, M. C.; Li, G. C.
Article Title: Requirement for Ku80 in growth and immunoglobulin V(D)J recombination
Abstract: THE DNA-dependent protein kinase (DNA-PK) is a mammalian serine/threonine kinase that is implicated in the repair of DNA double-strand breaks(1-4), DNA replication(1,5), transcription(6-8), and V(D)J recombination(9-12). To determine the role of the DNA-binding subunit of DNA-PK in vivo, we targeted Ku80 in mice. In mutant mice, T and B lymphocyte development is arrested at early progenitor stages and there is a profound deficiency in V(D)J rearrangement. Although Ku80(-/-) mice are viable and reproduce, they are 40-60% of the size of littermate controls. Consistent with this growth defect, fibroblasts derived from Ku80(-/-) embryos showed an early loss of proliferating cells, a prolonged doubling time, and intact cell-cycle checkpoints that prevented cells with damaged DNA from entering the cell-cycle. The unexpected growth phenotype suggests a new and important link between Ku80 and growth control.
Keywords: mice; gene; autoantigen; mutant; sensitivity; dependent protein-kinase; cell-line; catalytic subunit; strand-break-repair; dna end-binding
Journal Title: Nature
Volume: 382
Issue: 6591
ISSN: 0028-0836
Publisher: Nature Publishing Group  
Date Published: 1996-08-08
Start Page: 551
End Page: 555
Language: English
ACCESSION: WOS:A1996VB25800054
DOI: 10.1038/382551a0
PROVIDER: wos
PUBMED: 8700231
Notes: Article -- Source: Wos
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MSK Authors
  1. Gloria C Li
    132 Li
  2. Andre Nussenzweig
    18 Nussenzweig
  3. Vera Soares
    22 Soares
  4. Chang Hu Chen
    15 Chen
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