Loss of the catalytic subunit of the DNA-dependent protein kinase in DNA double-strand-break-repair mutant mammalian cells

S. R. Peterson, A. Kurimasa, M. Oshimura, W. S. Dynan, E. M. Bradbury, D. J. Chen

Research output: Contribution to journalArticle

260 Citations (Scopus)

Abstract

The DNA-dependent protein kinase (DNA-PK) consists of three polypeptide components: Ku-70, Ku-80, and an ≃350-kDa catalytic subunit (p350). The gene encoding the Ku-80 subunit is identical to the x-ray-sensitive group 5 complementing gene XRCC5. Expression of the Ku-80 cDNA rescues both DNA double-strand break (DSB) repair and V(D)J recombination in group 5 mutant cells. The involvement of Ku-80 in these processes suggests that the underlying defect in these mutant cells may be disruption of the DNA-PK haloenzyme. In this report we show that the p350 kinase subunit is deleted in cells derived from the severe combined immunodeficiency mouse and in the Chinese hamster ovary cell line V-3, both of which are defective in DSB repair and V(D)J recombination. A centromeric fragment of human chromosome 8 that complements the scid defect also restores p350 protein expression and rescues in vitro DNA-PK activity. These data suggest the scid gene may encode the p350 protein or regulate its expression and are consistent with a model whereby DNA-PK is a critical component of the DSB-repair pathway.

Original languageEnglish (US)
Pages (from-to)3171-3174
Number of pages4
JournalProceedings of the National Academy of Sciences of the United States of America
Volume92
Issue number8
StatePublished - 1995

Fingerprint

DNA-Activated Protein Kinase
Catalytic DNA
Double-Stranded DNA Breaks
Catalytic Domain
V(D)J Recombination
Genes
Severe Combined Immunodeficiency
Chromosomes, Human, Pair 8
Human Chromosomes
Cricetulus
Ovary
Proteins
Phosphotransferases
Complementary DNA
X-Rays
Cell Line
Peptides

Keywords

  • DNA repair
  • Ku protein
  • scid/scid mouse

ASJC Scopus subject areas

  • General
  • Genetics

Cite this

Loss of the catalytic subunit of the DNA-dependent protein kinase in DNA double-strand-break-repair mutant mammalian cells. / Peterson, S. R.; Kurimasa, A.; Oshimura, M.; Dynan, W. S.; Bradbury, E. M.; Chen, D. J.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 92, No. 8, 1995, p. 3171-3174.

Research output: Contribution to journalArticle

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AU - Kurimasa, A.

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AU - Dynan, W. S.

AU - Bradbury, E. M.

AU - Chen, D. J.

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