title: A link between double-strand break-related repair and V(D)J recombination: the scid mutation.
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.
authors.affiliation: Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, MA 02115.
authors.forename: E A
authors.initials: EA
authors.lastname: Hendrickson
authors.forename: X Q
authors.initials: XQ
authors.lastname: Qin
authors.forename: E A
authors.initials: EA
authors.lastname: Bump
authors.forename: D G
authors.initials: DG
authors.lastname: Schatz
authors.forename: M
authors.initials: M
authors.lastname: Oettinger
authors.forename: D T
authors.initials: DT
authors.lastname: Weaver
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001761:Bleomycin / Q000494:pharmacology; D004249:DNA Damage; D004260:DNA Repair; D005347:Fibroblasts / Q000378:metabolism / Q000528:radiation effects; D007153:Immunologic Deficiency Syndromes / Q000235:genetics*; D007700:Kinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D011995:Recombination, Genetic
chemical_list: D001761:Bleomycin