A link between double-strand break-related repair and V(D)J recombination: The scid mutation

E. A. Hendrickson, X. Q. Qin, E. A. Bump, D. G. Schatz, M. Oettinger, D. T. Weaver

Research output: Contribution to journalArticlepeer-review

281 Scopus citations

Abstract

We show here that mammalian site-specific recombination and DNA-repair pathways share a common factor. The effects of DNA-damaging agents on cell lines derived from mice homozygous for the scid (severe combined immune deficiency) mutation were studied. Surprisingly, all scid cell lines exhibited a profound hypersensitivity to DNA-damaging agents that caused double-strand breaks (x-irradiation and bleomycin) but not to other chemicals that caused single-strand breaks or cross-links. Neutral filter elution assays demonstrated that the x-irradiation hypersensitivity could be correlated with a deficiency in repairing double-strand breaks. These data suggest that the scid gene product is involved in two pathways: DNA repair of random double-strand breaks and the site-specific and lymphoid-restricted variable-(diversity)-joining [V(D)J] DNA rearrangement process. We propose that the scid gene product performs a similar function in both pathways and may be a ubiquitous protein.

Original languageEnglish (US)
Pages (from-to)4061-4065
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume88
Issue number10
DOIs
StatePublished - 1991

Keywords

  • DNA repair
  • x-irradiation

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