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

Journal Article · · Proceedings of the National Academy of Sciences of the United States of America; (USA)
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.
OSTI ID:
5760361
Journal Information:
Proceedings of the National Academy of Sciences of the United States of America; (USA), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (USA) Vol. 88:10; ISSN PNASA; ISSN 0027-8424
Country of Publication:
United States
Language:
English